Intracorporeal expandable shock wave reflector

ABSTRACT

An intracorporeal pressure shock wave includes an expandable pressure shock wave reflector at the distal end of an intracorporeal catheter to direct shock waves from a shock wave generator within a human or animal blood vessel or body lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 14/874,650, filed Oct. 5, 2015, now U.S. Pat. No.10,639,051, which is a continuation application of U.S. patentapplication Ser. No. 14/272,155, filed May 7, 2014, now U.S. Pat. No.10,058,340, which is a divisional application of U.S. patent applicationSer. No. 14/036,461 filed on Sep. 25, 2013, now U.S. Pat. No. 9,161,768,which is a divisional application of U.S. patent application Ser. No.12/832,932 filed Jul. 8, 2010, now U.S. Pat. No. 8,556,813, which claimsthe benefit of priority of U.S. Provisional Application No. 61/223,919filed Jul. 8, 2009, which are all incorporated herein by reference.

SUMMARY OF THE INVENTION

The efficacy of pressure shock waves for treatment of skin, tissue (softand hard), and vasculature may be based on a number of factors,including without limitation: (a) cavitation during tensile phase whichcan break tissue bonds, blood vessels plaque, and other target area; (b)beneficial effects on reducing inflammation in soft tissue. includinghelping with reducing edema or helping to reduce inflammation aftersurgical intervention on or close proximity to natural human/animalconduits/lumens or after blood vessels' stenting andangioplasty—technologies that produce inflammation (hyperplasia); (c)pressure shock waves may dissolve lipids which are an important part ofthe plaque structure or for reducing the effects of cellulite or forreducing body fat in general (body sculpting); (d) pressure shock wavescan reduce tissue spasm/contraction and blood vessel's spasm, such aswithout limitation after stenting and angioplasty; (e) pressure shockwaves can act on peripheral nerves to reduce pain or promote nerveregeneration and repair; (f) pressure shock waves produce vesselsdilation, which can help with penetration of the vessels' obstructionsusing guide wires and can enhance blood circulation to the treatmentareas; (g) pressure shock waves can stimulate the growth of newcapillaries and activate dormant stem cells and angiogenesis factors,which can enhance collateral blood circulation to reduce poor bloodcirculation; (h) certain dosages may inhibit smooth cellsproliferations, which can prevent restenosis (blockage of the vesselsthat were already treated due to smooth muscle cells proliferationstriggered by inflammation produced either by angioplasty or stenting);(i) pressure shock waves can stimulate the growth of hard and softtissues, which can be used in the treatment of bone fractures, producingbone fusion, repair of tears in cartilage, muscle, skin, ligaments,tendons, and the like; (j) pressure shock waves can reverse hard andsoft tissue necrosis through increases blood circulation and recruitingof growth factors; (k) pressure shock waves can prevent adhesionsbetween organs after surgeries in the abdominal, muscular, chest areas,and the like; (l) pressure shock waves can break down scar tissue andfibrotic tissue formed around medical incision; (m) pressure shock wavescan be easily transmitted in saline solutions, blood, contrast media,liquid drugs—such liquids and body fluids not only transmit the pressureshock waves, but cavitation may be generated such as to break plaque,break cellular, bacteria and viruses membranes or push DNA inside cells;and (n) pressure shock waves can avoid a thermal effect that can altertissue in general or blood vessels' cells' structure or increase therisk of blood coagulation. This thermal effect represents the maindrawback with treatments for blood vessels using low or high frequencyultrasound (focused or non-focused), radio frequency, microwaves, andthe like. The lack of thermal effect recommends this treatment ofcirculatory problems (lack of coagulation effects and the capacity ofdestroying plaques) and also for “cold” controlled ablation of unwantedbone or tissue growths, including benign or malignant tumors.

Based on one or more of the foregoing factors, pressure shock wavetreatment may be used independently, or in combination with othermedical treatments to promote synergetic effects before, during andafter other medical therapies. Some examples of pressure shock waveapplications include: high energy pressure shock waves to destroy bloodvessels plaque; high energy pressure shock waves to penetrate totalocclusions of the blood vessels or natural human/animal conduits/lumens;low to medium energy pressure shock waves to treat vulnerable plaquefrom the blood vessels; high energy pressure shock waves to dissolveblood clots (thrombus or embolus) from the blood vessels or naturalhuman/animal conduits/lumens; low to medium energy pressure shock wavesto treat the muscle of the heart (after cardiac infarction) incombination with stem cells; genes or proliferation agents for musclegrowth and/or angiogenesis or vasculogenesis; low to medium energypressure shock waves to improve functionality of muscles that activateheart valves; high energy pressure shock waves to remove fluidaccumulation in heart sack; high energy pressure shock waves to helpwith pacemakers leads extraction by producing their loosening beforetheir removal from heart muscle; low to medium energy pressure shockwaves to promote accelerated healing after angioplasty or stenting usingmetal bare stents or drug eluting stents; low to medium energy pressureshock waves to treat in-stent restenosis (blockage of the blood vesselafter stenting due to regrowth of the smooth muscle; high energypressure shock waves combined with drugs to prevent smooth muscleformation after angioplasty or stenting; high energy pressure shockwaves combined with dissolution agents for blood clots (thrombus orembolus) elimination from blood vessels or artificially createdshunts/fistulas or from natural human/animal conduits/lumens; highenergy pressure shock waves combined with drugs to enhance plaqueremoval from blood vessels; high energy pressure shock waves combinedwith drugs to enhance and speed-up the elimination of total occlusionsfrom blood vessels or natural human/animal conduits/lumens; low energypressure shock waves in combination with drugs to stabilize vulnerableplaque from the blood vessels; low to medium energy pressure shock wavesto treat vessel's wall to prevent formation of arterial aneurysms orvaricose veins (enlarged and/or twisted veins); low to medium energypressure shock waves to treat vessel's or natural human/animalconduits/lumens wall for chronic inflammation; medium to high energypressure shock waves to treat burns, to heal or improve healing of acuteand chronic wounds, to enhance blood circulation/perfusion, reduceinflammation and edema and improve cosmetic aspect of the skin; mediumto high energy pressure shock waves to break fat cells and producecollagen fibers to reinforce skin for cellulite applications; medium tohigh energy pressure shock waves to promote body sculpting through fatreduction; low to medium energy pressure shock waves to promote skinrejuvenation through collagen creation and increased blood circulation;low to medium energy pressure shock waves to promote healing of thesurgical incisions; medium to high energy pressure shock waves toprevent/eliminate hyperthrophic lesions, organs adhesions, and fibrotictissue formations or capsular contracture around implants; low to mediumenergy pressure shock waves to improve the aesthetic aspect of the skinscar tissue (after open surgeries); low to medium energy pressure shockwaves to treat tissue in combination with stem cells, genes orproliferation agents for tissue growth and/or angiogenesis orvasculogenesis; medium to high energy pressure shock waves to treatunwanted tissue hyperplasia as benign prostate hyperplasia (BPH) and thelike; low and medium energy pressure shock waves to reduce edema andinflammation by pushing the by-products into lymphatic system; medium tohigh energy pressure shock waves to push excessive accumulation of lymphinto lymphatic system, thus preventing lymph-edema; medium to highenergy pressure shock waves to promote the repair of lymphatic vessels;medium to high energy pressure shock waves to destroy/crack hard tissues(for example bone spurs, heterotopic ossifications, calcifications,plaque formation on teeth, etc.) due to compressive forces incombination with cavitation microjets; low to medium energy pressureshock waves to stimulate angiogenesis and vasculogenesis; low to mediumenergy pressure shock waves to treat muscles for pain, tear, contractureand stimulate muscle growth; high energy pressure shock waves to inhibitmuscle growth; low and medium energy pressure shock waves to interact atthe cellular level, to call for immune system and acute repairmechanism; low and medium energy pressure shock waves to treatinterstitial cystitis through cells stimulation and bladderre-epithelialization; low and medium energy pressure shock waves to callin of the stem cells or activate dormant stem cells for tissue repair;low to medium energy pressure shock waves to stimulate stem cellsformation at the donor site before harvesting, their proliferation,differentiation and enhance their effects after implantation; medium andhigh energy pressure shock waves to push DNA fragments, genes, etc.,inside cells that can generate different cellular reactions; high energypressure shock waves to activate and accelerate cellular apoptosis; highenergy pressure shock waves and especially cavitation jets canpenetrate/break cellular membranes and thus destroying cells usingnon-heat producing mechanisms (useful to selectively destroy cancercells); medium to high energy pressure shock waves to kill Gram positiveand Gram negative bacteria, viruses or destroy biofilms; medium to highenergy pressure shock waves to treat bacterial or abacterial prostatitis(chronic pelvic syndrome), through reduction of inflammation andstimulation of immune system; medium to high energy pressure shock wavesto enhance/accelerate the treatment of fungal infections in conjunctionwith appropriate medication; medium energy pressure shock waves to treataseptic loosening of human replacement prosthesis; high energy pressureshock waves to help with human replacement prostheses, implants, stentsextraction by producing their loosening before their removal from thehuman body; low to medium energy pressure shock waves to stimulate thegrowth of soft tissues, which can be used in the repair of tears incartilage, muscle, skin, ligaments, tendons, and the like; medium tohigh energy pressure shock waves to stimulate the growth of hardtissues, which can be used in the treatment of acute bone fractures andbone non-unions, to produce backbone fusions, and the like; low tomedium pressure shock waves to treat auto-immune diseases as SystemicLupus Erythematosus, Scleroderma, Crohn's Disease, Dermatomyositis, andthe like; medium to high energy pressure shock waves to treat skininfections, high energy pressure shock waves to fragment biodegradablestructures in small pieces to allow the easy absorption by the body; lowto medium pressure shock waves to reduce pain or promote nerveregeneration and repair; low to medium energy pressure shock waves tokill parasites, harmful micro-organisms, and the like; and medium tohigh energy pressure shock waves to deliver high concentration drugsinside the tissue from patches and subcutaneous biodegradable pouches.

As used herein, High Energy pressure shock waves generate a flux densityhigher than 0.3 mJ/mm².

As used herein, Medium Energy pressure shock waves generate a fluxdensity less than 0.3 mJ/mm² and higher than 0.1 mJ/mm².

As used herein, Low Energy pressure shock waves generate a flux densitylower than 0.1 mJ/mm².

The flux density combined with frequency of the shots (1-15 Hz) and thenumber of shocks per one session (500-50,000) can dictate the energyoutcome of shock wave treatments.

In general, High Energy treatments should be able to deliver in onesession in the targeted treatment area higher than 1000 Joules ofenergy, Medium Energy treatments between 100 and 1000 Joules and LowEnergy treatments less than 100 Joules.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of pressure shock waves applied to anocclusion in one embodiment of the present invention.

FIG. 2 is a schematic diagram of shock wave applicator reflectors'orientations relative to the skin and an occlusion target in oneembodiment of the present invention.

FIG. 3 is a schematic diagram of shock wave applicator reflectors'orientations relative to an occlusion target in one embodiment of thepresent invention.

FIG. 4 is a schematic diagram of shock wave applicator reflectors'orientations relative to an occlusion target in one embodiment of thepresent invention.

FIG. 5A is a schematic diagram of shock wave applicator reflectors'orientations relative to an occlusion target in one embodiment of thepresent invention.

FIG. 5B is a schematic diagram of a shock wave applicator's orientationrelative to a blood vessel target and bone in one embodiment of thepresent invention.

FIG. 6 is a schematic diagram of an elongated shock wave applicatorreflector with multiple discharge points in one embodiment of thepresent invention.

FIG. 7 is a schematic diagram of a shock wave applicator's orientationrelative to an occlusion target in one embodiment of the presentinvention.

FIG. 8A is a schematic diagram of shock wave applicators with anauxiliary placement device relative to a blood vessel target in oneembodiment of the present invention.

FIG. 8B is a schematic diagram of shock wave applicators with anauxiliary placement device relative to a blood vessel target in oneembodiment of the present invention.

FIG. 9 is a schematic diagram of a shock wave reflectors' orientationrelative to a treated occlusion and including debris flushing in oneembodiment of the present invention.

FIG. 10 is a schematic diagram illustrating different treatment depthswith a shock wave applicator reflector relative to skin in oneembodiment of the present invention.

FIG. 11 is a schematic diagram of a movable shock wave applicatorincluding a wheel positioned relative to skin and a target occlusion inone embodiment of the present invention.

FIG. 12A is a schematic diagram of a pivotable shock wave applicatorincluding bellows in one embodiment of the present invention.

FIG. 12B is a schematic diagram of a bottom plan view of the applicatorof FIG. 12A in one embodiment of the present invention.

FIG. 13 is a schematic diagram of plaque to be treated in a blood vesselin one embodiment of the present invention.

FIG. 14A is a schematic diagram of a shock wave applicator positioned totreat vascular plaque in one embodiment of the present invention.

FIG. 14B is a schematic diagram of a shock wave applicator positioned totreat vascular plaque in one embodiment of the present invention.

FIG. 15A is a schematic diagram of a shock wave applicator and debrisbasket positioned to treat vascular plaque in one embodiment of thepresent invention.

FIG. 15B is a schematic diagram of a shock wave applicator and occlusionballoon positioned to treat vascular plaque in one embodiment of thepresent invention.

FIG. 16A is a schematic diagram of a shock wave applicator and occlusionballoons positioned to treat vascular plaque in one embodiment of thepresent invention.

FIG. 16B is a schematic diagram of a shock wave applicator and occlusionballoons positioned to treat vascular plaque in one embodiment of thepresent invention.

FIG. 17 is a schematic diagram of a shock wave applicator positioned totreat tissue in blood vessel with a stent in one embodiment of thepresent invention.

FIG. 18 is a schematic diagram of an artery and vein with an artificialvessel in one embodiment of the present invention.

FIG. 19 is a schematic diagram of a shock wave applicator positioned totreat in-stent restenosis in one embodiment of the present invention.

FIG. 20 is a schematic diagram of a shock wave applicator having anelongated aperture and positioned for treatment of a heart in oneembodiment of the present invention.

FIG. 21A is a schematic diagram of an elongated shock wave applicatorreflector with multiple discharge points in one embodiment of thepresent invention.

FIG. 21B is a schematic diagram of an elongated shock wave applicatorreflector with multiple discharge points and activation button in oneembodiment of the present invention.

FIG. 22 is a schematic diagram of a shock wave applicator with angledreflectors' portions' geometries in one embodiment of the presentinvention.

FIG. 23A is a schematic diagram of a shock wave applicator including areversed ellipsoid reflector in one embodiment of the present invention.

FIG. 23B is a schematic diagram of a top plan view of an aperture of ashock wave applicator including a reversed ellipsoid reflector in oneembodiment of the present invention.

FIG. 24A is a schematic diagram of a shock wave applicator positionedfor extracorporeal treatment of a heart in one embodiment of the presentinvention.

FIG. 24B is a schematic diagram of a shock wave applicator positionedfor extracorporeal treatment of a heart in one embodiment of the presentinvention.

FIG. 25 is a schematic diagram illustrating travel of shock wavesthrough materials of the same and different acoustic impedances in oneembodiment of the present invention.

FIG. 26 is a schematic diagram of shock applicators positioned fortreating and loosening pacemaker leads from heart tissue in oneembodiment of the present invention.

FIG. 27A is a schematic diagram of a pivotable shock wave applicatorincluding bellows in one embodiment of the present invention.

FIG. 27B is a schematic diagram illustrating a bottom plan view apivotable shock wave applicator including bellows and with vacuumsuction in one embodiment of the present invention.

FIG. 28 is a schematic diagram of a movable shock wave applicatorincluding a roller for treating tissue layers in one embodiment of thepresent invention.

FIG. 29 is a schematic diagram of a movable shock wave applicatorincluding multiple rollers with vacuum suction to treat target tissue inan embodiment of the present invention.

FIG. 30A is a schematic diagram of a biodegradable stent in oneembodiment of the present invention.

FIG. 30B is a schematic diagram of a stent luminal radial reinforcementhaving foldable walls in one embodiment of the present invention.

FIG. 31 is a schematic diagram of a shock wave applicator positionedwith a focal zone intersecting a stent in a blood vessel in oneembodiment of the present invention.

FIG. 32A is a schematic diagram of a top plan view of a drug-releasingpouch system in one embodiment of the present invention.

FIG. 32B is a schematic diagram of a side view of a drug-releasing pouchsystem in one embodiment of the present invention.

FIG. 33 is a schematic diagram of a side view of a shock wave applicatorpositioned with a focal zone at a drug-releasing pouch system in a bodyin one embodiment of the present invention.

FIG. 34 is a schematic diagram of both over-the-wire and rapid-exchangesolutions of guide wires and catheters in one embodiment of the presentinvention.

FIG. 35 is a schematic diagram of an intracorporeal shock wave catheterin one embodiment of the present invention.

FIG. 36A is a schematic diagram of an intracorporeal shock wave catheterin a blood vessel in one embodiment of the present invention.

FIG. 36B is a schematic diagram of a cross-sectional view along AA ofFIG. 36A of an intracorporeal shock wave catheter in one embodiment ofthe present invention.

FIG. 37 is a schematic diagram of an intracorporeal shock wave catheterand occlusion balloon system in a blood vessel in one embodiment of thepresent invention.

FIG. 38 is a schematic diagram of an intracorporeal shock wave catheterand debris collection basket system in a blood vessel in one embodimentof the present invention.

FIG. 39 is a schematic diagram of an intracorporeal shock wave catheterand multiple occlusion balloons system with a membrane protecting areflector in a blood vessel in one embodiment of the present invention.

FIG. 40 is a schematic diagram of an intracorporeal shock wave catheterand multiple occlusion balloons system without a membrane protecting areflector in a blood vessel in one embodiment of the present invention.

FIG. 41 is a schematic diagram of an intracorporeal shock wave catheterwith a reflector incorporated in an occlusion balloon in one embodimentof the present invention.

FIG. 42 is a schematic diagram of aneurysms' locations in one embodimentof the present invention.

FIG. 43 is a schematic diagram of an intracorporeal shock wave catheterincluding multiple reflectors in one embodiment of the presentinvention.

FIG. 44 is a schematic diagram of an intracorporeal shock wave catheterincluding multiple reflectors disposed in a non-occlusion balloon in oneembodiment of the present invention.

FIG. 45 is a schematic diagram of an intracorporeal shock wave catheterincluding multiple reflectors disposed in a non-occlusion balloonwithout contacting an aneurysm in one embodiment of the presentinvention.

FIG. 46 is a schematic diagram of a catheter reflector having multipledischarge points in one embodiment of the present invention.

FIG. 47A is a schematic diagram of an intracorporeal shock wave catheterwith a frontal reflector positioned for treating an occlusion in a bloodvessel in one embodiment of the present invention.

FIG. 47B is a schematic diagram of an intracorporeal shock wave catheterwith a frontal reflector positioned for treating an occlusion in a bloodvessel in one embodiment of the present invention.

FIG. 47C is a schematic diagram of an intracorporeal shock wave catheterwith an extendible frontal reflector positioned for treating anocclusion in a blood vessel in one embodiment of the present invention.

FIG. 48 is a schematic diagram of an expandable stent and intracorporealshock wave catheter in one embodiment of the present invention.

FIG. 49A is a schematic diagram of an expandable tulip reflector of anintracorporeal shock wave catheter in closed position in one embodimentof the present invention.

FIG. 49B is a schematic diagram of an expandable tulip reflector of anintracorporeal shock wave catheter in an open position in one embodimentof the present invention.

FIG. 49C is a schematic diagram of an expandable tulip reflector of anintracorporeal shock wave catheter in closed position in a blood vesseland relative to an occlusion one embodiment of the present invention.

FIG. 49D is a schematic diagram of an expandable tulip reflector of anintracorporeal shock wave catheter in an open position in a blood vesseland relative to an occlusion one embodiment of the present invention.

FIG. 49E is a schematic diagram of an expandable tulip reflector of anintracorporeal shock wave catheter in closed position in a blood vesseland relative to a treated occlusion one embodiment of the presentinvention.

FIG. 50A is a schematic diagram of a first step of advancing a tandem ofguide catheter and tulip reflector in one embodiment of the invention.

FIG. 50B is a schematic diagram of a second step of advancing a tandemof guide catheter and tulip reflector in one embodiment of theinvention.

FIG. 50C is a schematic diagram of a third step of advancing a tandem ofguide catheter and tulip reflector in one embodiment of the invention.

FIG. 50D is a schematic diagram of a fourth step of advancing a tandemof guide catheter and tulip reflector in one embodiment of theinvention.

FIG. 51 is a schematic diagram of an intracorporeal shock wave devicetreating a fat deposit in one embodiment of the present invention.

FIG. 52A is a schematic diagram of an intracorporeal shock wave devicetreating a fat deposit with a spherical reflector in one embodiment ofthe present invention.

FIG. 52B a schematic diagram of an intracorporeal shock wave devicetreating a fat deposit with an extendible reflector in one embodiment ofthe present invention.

FIG. 53 is a schematic diagram of an intracorporeal shock wave deviceand extracorporeal shock wave device treatment system in one embodimentof the present invention.

FIG. 54A is a schematic diagram of an intracorporeal shock wave catheterhaving radially generated shock waves in one embodiment of the presentinvention.

FIG. 54B a schematic diagram with a front cross-sectional view along AAof FIG. 54A of an intracorporeal shock wave catheter having non-focused,radially generated shock waves in one embodiment of the presentinvention.

FIG. 55A is a schematic diagram of an intracorporeal shock wave catheterhaving planar generated shock waves in one embodiment of the presentinvention.

FIG. 55B is a schematic diagram of an intracorporeal shock wave catheterhaving radially generated shock waves in one embodiment of the presentinvention.

FIG. 55C is a schematic diagram of a cross-section front view along AAof FIG. 55B of n intracorporeal shock wave catheter having radiallygenerated shock waves in one embodiment of the present invention.

FIG. 56 is a graph of pressure phases of a shock wave in an embodimentof the present invention.

FIG. 57A is a schematic diagram of a full ellipsoidal reflectorgenerating a spherical focal volume in one embodiment of the presentinvention.

FIG. 57B is a schematic diagram of a 50% ellipsoidal reflectorgenerating a focal volume in one embodiment of the present invention.

FIG. 57C is a schematic diagram of a 35% ellipsoidal reflectorgenerating a focal volume in one embodiment of the present invention.

FIG. 57D is a schematic diagram of a 20% ellipsoidal reflectorgenerating a focal volume in one embodiment of the present invention.

FIG. 58A is a schematic illustration of a reflector having a largesemi-axis (c) and small semi-axis (b) with a c/b ratio between 1.1 and1.6 in one embodiment of the present invention.

FIG. 58B is a schematic illustration of a reflector having a largesemi-axis (c) and small semi-axis (b) with a c/b ratio between 1.6 and2.0 in one embodiment of the present invention.

FIG. 58C is a schematic illustration of a reflector having a largesemi-axis (c) and small semi-axis (b) with a c/b ratio greater than 2.0in one embodiment of the present invention.

FIG. 59 is a schematic diagram illustrating a comparison of focalvolumes versus reflector aperture area in one embodiment of the presentinvention.

FIG. 60 is a schematic diagram of a reflector with a combination ofgeometries in one embodiment of the present invention.

FIG. 61A is a schematic diagram of a conventional reflector geometrywith a long axis of symmetry in one embodiment of the present invention.

FIG. 61B is a schematic diagram of a reversed reflector geometry with ashort axis of symmetry in one embodiment of the present invention.

FIGS. 62A and 62B are schematic diagrams of a reversed reflector with acombination of geometries in embodiments of the present invention.

FIG. 63 is a schematic diagram of a multiple combined reflectors in oneembodiment of the present invention.

FIG. 64A is a schematic diagram of a shock wave applicator includingmultiple reflectors in two perpendicular directions in one embodiment ofthe present invention.

FIG. 64B is a schematic diagram of a cross-sectional side view along AAof FIG. 64A of a shock wave applicator including multiple reflectors intwo perpendicular directions in one embodiment of the present invention.

FIG. 65A is a schematic diagram of a cross-sectional side view of a halfsphere dish having multiple reflectors and discharge points in oneembodiment of the present invention.

FIG. 65B is a schematic diagram of a bottom plan view of a half spheredish having multiple reflectors and discharge points in one embodimentof the present invention.

FIG. 65C is a schematic diagram of a partial perspective view from aboveof a half sphere dish having multiple reflectors and discharge points inone embodiment of the present invention.

FIG. 66A is a schematic diagram of multiple reflectors arranged on adish in one embodiment of the present invention.

FIG. 66B is a schematic diagram of multiple reflectors arranged on adish in one embodiment of the present invention.

FIG. 67 is a schematic diagram of a multiple shock wave applicatortreatment system in one embodiment of the present invention.

FIG. 68A is a schematic diagram of a multiple shock wave applicatortreatment system having positioning sensors in one embodiment of thepresent invention.

FIG. 68B is a schematic diagram of a sensor block and positioningsensors of a shock wave applicator in one embodiment of the presentinvention.

FIG. 68C is a schematic diagram of a sensor block and positioningsensors of a shock wave applicator in one embodiment of the presentinvention.

FIG. 69 is a schematic diagram of a shock wave applicator system withpositioning sensors in one embodiment of the present invention.

FIG. 70A is a schematic diagram of a shock wave applicator system withpositioning sensors in one embodiment of the present invention.

FIG. 70B is a schematic diagram of a shock wave applicator system withpositioning sensors in one embodiment of the present invention.

FIG. 70C is a schematic diagram of a shock wave applicator system withpositioning sensors in one embodiment of the present invention.

FIG. 71 is a schematic diagram of a shock wave applicator systemincluding software-controlled positioning patterns in one embodiment ofthe present invention.

FIG. 72 is a schematic diagram of a shock wave applicator systemincluding liquid sprayer in one embodiment of the present invention.

FIG. 73 is a schematic diagram illustrating points on a plane in oneembodiment of the present invention.

FIG. 74A is a schematic diagram of a shock wave applicator system withan applicator and positioning holder in one embodiment of the presentinvention.

FIG. 74B is a schematic diagram of a shock wave applicator system withan applicator and positioning holder in one embodiment of the presentinvention.

FIG. 75A is a schematic diagram of a positioning holder plane of a shockwave applicator system at a surface of a body in one embodiment of thepresent invention.

FIG. 75B is a schematic diagram of a positioning holder plane of a shockwave applicator system above a surface of a body in one embodiment ofthe present invention.

FIG. 75C is a schematic diagram of a positioning holder plane of a shockwave applicator system below a surface of a body in one embodiment ofthe present invention.

FIG. 76A is a schematic diagram of a shock wave applicator system holderwith a connector to connect to another holder in one embodiment of thepresent invention.

FIG. 76B is a schematic diagram of a ball and hinge interconnectionbetween shock applicator system holder in one embodiment of the presentinvention.

FIG. 77 is a schematic diagram of a ball and hinge interconnectionbetween shock applicator system holder in one embodiment of the presentinvention.

FIG. 78A is a schematic diagram of an interconnected chain of shock waveapplicator system holders in one embodiment of the present invention.

FIG. 78B is a schematic diagram an interconnected chain of shock waveapplicator system holders in one embodiment of the present invention.

FIG. 79A is a schematic diagram of a reversed reflector geometry in oneembodiment of the present invention.

FIG. 79B is a schematic diagram of a reversed reflector geometry in oneembodiment of the present invention.

FIG. 80 is a schematic diagram of reflector including reversed geometryin one embodiment of the present invention.

FIG. 81 is a schematic diagram of a reflector including multipledischarge points in one embodiment of the present invention.

FIGS. 82A-93B are COMSOL simulation graphs showing the propagation ofshock wave fronts for resulting from shifting shock wave initiationpoint (Fi) in embodiments of the present invention.

FIGS. 94A is a schematic diagram of the focal volume relative to a firstposition of shock wave discharge location within a reflector in oneembodiment of the present invention.

FIG. 94B is a schematic diagram of the focal volume relative to a secondposition of shock wave discharge location within a reflector in oneembodiment of the present invention.

FIG. 95 is a schematic diagram of a shock wave applicator includingmovable electrode in one embodiment of the present invention.

FIG. 96 is a schematic diagram of a reversed reflector with focal pointshift in one embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

In embodiments of the invention, the application of pressure shock wavesfrom the outside of the body (extracorporeal) can be used for a varietyof applications that include without limitation:

removal of leads from heart muscle for pacemakers;

muscle regeneration (heart)—after myocardial infection using onlypressure shock waves or in combination with stem cells, genes orproliferation agents for muscle growth and/or angiogenesis orvasculogenesis;

treatment to improve functionality of muscles that activate heart valvesto improve heart valves functioning;

removal of fluid build-up around heart;

treatment of total occlusions for all blood vessels dimensions (notlimited by the vessel dimension) to eliminate critical limb ischemia(CLI) effects and peripheral arterial disease (PAD) symptoms;

treatment to inhibit inflammation or smooth muscle formation insidevessels;

treatment to regenerate circulation to ischemic tissues throughelimination of blood vessels stenosis and stimulation of small bloodvessels/capillaries formation to reduce the effects or eliminatecritical limb ischemia (CLI) effects and peripheral arterial disease(PAD) symptoms;

removal of blood vessels plaque accumulation;

enhancement of drug delivery to blood vessels walls;

stabilization of the vulnerable plaques of the blood vessels, incombination with drugs;

treatment to reduce inflammation post angioplasty and stenting (barestents or drug eluting stents) of the blood vessels to promoteaccelerated healing;

treatment to reduce chronic inflammation of the blood vessels or otherconduits of the human and animal bodies;

treatment of in-stent restenosis for blood vessels with pressure shockwaves alone or combined with drugs to prevent smooth muscle formationafter angioplasty or stenting;

removal of blood clots (thrombus or embolus) from blood vessels ornatural human/animal conduits/lumens;

prevention treatment to reduce the blood vessels spasm after angioplastyand stenting or of spasms of the natural/animal conduits/lumens ormuscle spasms and contracture (for example produce by cerebral palsy);

treatment of occluded artificial shunts/fistulas-treatment of totalocclusions or stenosis of natural human/animal conduits/lumens usingonly pressure shock waves or in combination with drugs;

treatment of occluded grafts (bypass grafts—natural or artificial);

treatment for blood clots removal from veins without destroying thevalves present in veins;

treatment of varicose veins;

treatment to improve cosmetic aspect of the “spider veins”;

enhancement of collateral blood flow around compromised vessels;

treatment of edema and inflammation by pushing the by-products intolymphatic system;

treatment to push excessive accumulation of lymph into lymphatic system,thus preventing lymph-edema;

promotion of lymphatic vessels repair;

treatment of burns, to heal or improve healing of acute and chronicwounds, to enhance blood circulation/perfusion, reduce inflammation andedema and improve cosmetic aspect of the skin;

cosmetic treatments based on destroying the fat cells and pushing theminto lymphatic system for elimination (cellulite, body sculpting, etc.);

treatment to reinforce of the skin through collagen formation andincreased blood circulation;

treatment for skin rejuvenation;

treatment to improve the cosmetically aspect of the skin scars;

treatment of internal fibrotic tissue, hyperthrophic lesions, and organadhesions generated post surgeries or capsular contracture aroundimplants;

treatment to repair tissues as bones, teeth, cartilage, tendons,ligaments, muscles, etc., which can be used in the treatment of bonefractures, producing spine fusion, repair of partial or total tears incartilage, muscle, ligaments, tendons, etc.;

regeneration of necrotic tissues as necrotic bone, necrotic skin, etc.and restoration of normal blood circulation through angiogenesis andrecruiting of growth factors;

tissue regeneration using only pressure shock waves or in combinationwith stem cells, genes or proliferation agents for tissue growth and/orangiogenesis or vasculogenesis;

destruction of unwanted hard tissues (for example bone spurs,heterotopic ossifications, calcifications, plaque formation on teeth,etc.);

treatment to destroy cancer tumors or unwanted benign tissue hyperplasia(as benign prostate hyperplasia or BPH) using a “normal body temperatureablation” approach;

treatment to enhance toxicity of certain drugs used for cancertreatment;

treatment to activate dormant stem cells for tissue repair;

treatment to stimulate stem cells formation at the donor site beforeharvesting;

treatment of stem cells to enhance their in vitro proliferation;

treatment of stem cells to promote their differentiation;

treatment of stem cells to enhance their effects after implantation;

treatment to stimulate the regeneration of soft tissue as ininterstitial cystitis (lining of the bladder wall);

treatment to kill Gram positive and Gram negative bacteria, viruses ordestroy biofilms;

treatment for bacterial or abacterial prostatitis (chronic pelvicsyndrome), through reduction of inflammation and stimulation of immunesystem;

treatment of fungal infections in conjunction with appropriatemedication;

treatment of pain associated with inflammation and nerve stimulation(analgesic effect);

treatment of nerve degeneration by promoting nerve regeneration andrepair;

targeted treatment for different viruses and bacteria or abnormal cellsfrom the living tissue;

treatment of ascetic loosening of human replacement prosthesis, toprevent their unwanted movement inside the implantation site;

in-vitro gene treatment to produce improved genetic material for thetreatment of different genetic affliction;

reduce the symptoms/effects and treat auto-immune diseases as SystemicLupus

Erythematosus, Ankylosing Spondylitis, Crohns Disease, Scleroderma,Dermatomyositis, etc.;

loosening of prostheses, stents, implants to allow easyextraction/removal from hard and soft tissue;

elimination of cysts;

treatment to kill parasites, harmful micro-organisms, etc.;

controlled fragmentation of biodegradable stents in small pieces toallow the easy absorption by the body after their function in the bloodvessels was accomplished and to avoid thrombosis of large pieces carrieddown the blood stream;

fragmentation of any internal biodegradable structures in small piecesafter its functional life was accomplished for easy absorption by thebody; and

delivery of high concentration drugs inside the tissue (organs, muscle,bones or dermis) from patches and subcutaneous biodegradable pouches.

In one embodiment of the invention, extracorporeal pressure shock wavesmay be used for treatment of a total blood vessel occlusion or a naturalhuman/animal conduit/lumen occlusion.

Total occlusions in the vascular system represent the formation ofplaque that totally occludes the blood vessels cross sections or can beproduced by accumulation of debris combined with wall inflammation forany natural human or animal conduit or lumen.

For blood vessels, the occlusions can have a soft or a hard cap at theirdistal or proximal ends. The most difficult to penetrate are the oneswith the hard cap. The occlusions with soft cap can be penetrated duringmanipulation of the guide wires by the physicians. Even so, not all thetime will the total occlusions with soft cap be penetrated, due to theirlong length or distal composition of the occlusion (beyond the softcap).

Numerous devices were developed to treat total occlusions for bloodvessels that can produce critical limb ischemia (reduced bloodcirculation and thus reduced tissue oxygenation down the blood flow,which can degenerate loss of distal limbs or parts of foot). Also, theblockage of the carotid arteries that bring oxygenated blood to thebrain can be damaging or fatal to brain functionality (blockage of bloodflow towards the brain can produce brain tissue ischemia, which cangenerate loss of functionality or death of brain cells).

Pressure shock waves can offer an extracorporeal approach for treatingtotal occlusions of blood vessels or from any natural human or animalconduits or lumens as non-invasive procedures. Referring to FIG. 1, thedestruction of total occlusions is mainly produced by cavitation, whichwould preferably be directed as perpendicular as possible on theocclusion cap 10. The extracorporeal approach typically directs atangles less than 90° but higher than 20°, depending on the position ofthe vessels 15 or natural human/animal conduit/lumen relatively to theskin.

The direction, such as direction 12 a or 12 b, used for focusing theshockwaves at an angle between 20°-70° relative to the surface of theocclusion cap 10, causes cavitation bubbles collapse to be orientedagainst the occlusion cap 10 and not tangential to it. To producecavitation in front of the occlusion cap 10, the reflector of thepressure shock waves device may have the focal volume concentrate aroundthe occlusion cap 10 (in other words the occlusion cap 10 intersects thefocal volume of the pressure shock waves applicator).

The pressure shock waves applicators can be focused, unfocused orradial. Referring to FIG. 2, the geometry of the reflectors 22, 24 canbe part of an ellipsoid, a sphere, a paraboloid or a combination ofthem. The pressure shock waves can be produced using electrohydraulic,piezoelectric, electromagnetic and by explosive or projectile means.

As can be seen from FIG. 2, when compared with reflector 22 and angle(α₁), the reflector 24 with a smaller angle (α₂) relatively to the skin28 is preferred due to a more efficient orientation of the microjetsproduced by the collapse of cavitation bubbles relatively to theocclusion 20 that needs to be treated. In general the orientations ofthe cavitation microjets coincide with the direction of the focal lineF₁F₂. This assumption can be applied for the treatment of any occlusion20 produced in a blood vessel 15 or any natural human/animalconduit/lumen from a body appendage 25 or a body generally.

As seen from FIGS. 3, 4, 5A and 5B, embodiments of the extracorporealreflectors to treat occlusions 20 includes inclined geometry toorientate the cavitation towards the occlusion cap 10. As can be seenfrom FIG. 3, the treatment of occlusion 20 from a blood vessel 15 thathas normal blood flow 39 blocked inside the appendage 25 can beperformed using confocal opposite applicators 30 and 32. Shock waveapplicator 30 includes a housing 40 including a reflector 22 disposedwithin the housing 40. Shock wave applicator 32 also includes a housing41 including a reflector 22 disposed within the housing 41. Theapplicators 30 and 32 can have a longitudinal movement 31 in order tocover the full length of the occlusion 20.

Dual applicators 30 and 32 can be used for the treatment of bloodvessels 15 from appendages 25, in an opposite position as seen in FIG. 3or in a mirror position as presented in FIG. 4.

The focal point F₂ can be set either in the proximal region 33 or distalregion 34 of the occlusion 20 (proximal region 33 is defined invasculature as the point close to the heart and distal region_34 isdefined as the point away from the heart). The correct position of thefocal point F2 can be assessed/visualized using ultrasound probes 37that can detect the super echoic regions produced by the cavitationinside the human/animal body. If the focal point is set in the distalregion 34, as seen from FIGS. 3 and 4, to prevent fragment fromocclusion 20 to flow down the stream, a debris collection basket 35 hasto be installed below the occlusion 20 through a distal incision. Thebasket 35 in some embodiments is not needed if the fragments are smallin size (less 1 mm). If the focal point is set in proximal region 33 tothe occlusion 20 (as seen in FIG. 5A), to avoid debris accumulation asuction catheter system can be used to eliminate the debris. The smoothcontact of the applicator 30 with the skin 28 is done via a cushion/gelpad 52 that can accommodate the curvature of the body appendages 25 orbody generally.

Because the cavitation in blood will develop slower than in water, thenumber of shocks should be increased accordingly to create thecavitational seeding of the blood in front of occlusion cap 10.

In general, for occlusions 20 of blood vessels 15 or naturalhuman/animal conduits/lumens, in order to work the applicators 30 mustbe set in a position to avoid the bones 54 (as presented in FIG. 5B),which will produce significant reflection of the pressure shock waves.The pressure shock waves after breaking the occlusion cap 10 can be alsoapplied inside the occlusions 20 to destroy their internal structure andthus restoring the normal passage way. The occlusions 20 of bloodvessels 15 can be penetrated by breaking their solid structures(calcifications) or by liquefying the fat trapped inside the occlusion20.

After the breaking of the occlusions cap 10 from blood vessels 15,penetration of the guide wire through the occlusion 20 occurs,especially if the other cap (the distal one) is not hard. This approachworks if the breakage of the occlusion 20 starts from proximal region 33towards distal region 34.

In case that F₂ is set on the proximal end of the occlusion 20 a guidewire might be present, which can potentially reflect the pressure shockwaves. In such case the guide wire is retrieved in the proximal region33 to a safe distance, to not interact with the pressure shock waves.

With long reflector 65 having an elongated shape (FIG. 6) and multipledischarge points 68 a longer occlusion 20 or a larger area (for cosmeticapplication) can be treated in one position of the applicator 30. Forendovascular field (peripheral blood vessels treatments), this shape isindicated for the long femoral artery obstructions or obstructions 20 ofthe below-the-knee blood vessels 15.

The energy delivered in treatment area of the reflector shown in FIG. 6is lower than a normal elliptical reflector due to reduction inreflecting area for the focused pressure shock waves (the largerreflective area is available to focus the pressure shock waves, thelarger the focal volume is and more energy is found in the focalvolume). The decrease in energy delivered to the treatment area withreflector shown in FIG. 6 can be compensated by increasing the number ofshocks and/or by increasing the discharge voltage in Fi for theelectrohydraulic applicators 30 or the energy setting (in general) forall type of pressure shock waves applicators 30 (electrohydraulic,piezoelectric, electromagnetic and by explosive or projectile means) .Also, in cardiovascular applications the penetration depth is dependenton the vessel 15 position inside the human body 27 and can vary from5-100 mm. For treatment of other natural human or animal conduits orlumens the penetration depth can vary between 30-200 mm. The penetrationdepth drives the depth of the reflector shape, which can be shallow forsuperficial application or very deep for application where the focus isdeeper inside the human body.

Extracorporeal pressure shock waves may be used to treat occlusions 20,stenosis (reduce of cross section area of a blood vessels 15 or naturalhuman or animal conduits or lumens) and blood clot formation in bloodvessels 15 (veins and arteries) or natural human or animal conduits orlumens while avoiding limitations for treatment based on vessel 15 ornatural conduit/lumen size. This treatment improves over otherprocedures used to treat occlusions 20 (invasive procedures) for bloodvessels 15 that are physically limited by the catheter dimensions(tubular devices that carry stents inside the human body arteries orhave balloons at the distal end that are used to get to the occlusionarea). After the occlusions 20 of the blood vessels 15 are opened, othertechnologies used to re-establish the normal blood vessel cross-section(such as angioplasty and stenting) are also limited by the inability tobe used for blood vessels 15 smaller than 2 mm in diameter size.

Bones 54 can be an obstacle for pressure shock waves'penetration/propagation. For treatments in the blood vessels 15 of thehead area, the skull bone can be penetrated, although considerationnecessarily should be given as to what energy can be used and what isthe behavior of pressure shock waves transmitted through the skull boneand their interaction with the brain.

In general, the speed of sound (speed of propagation of the pressureshock waves) is different for each type of human or animal tissueincluding: skin at 1,600 m/s, water at 1,500 m/s, fat at 1,400 m/s,muscle at 1,600 m/s, bone at 3,500 m/s and dry air at 21° C. is 344 m/s.

Large differences in speed of sound or acoustic impedance (speed ofsound multiplied by density of the substance) in different tissue layers(for example between soft tissue and bone or soft tissue and air) mayresult in reflections of the pressure shock waves. Such reflections caninterrupt or change direction of the pressure shock waves and thus theiraction in the focal volume around F₂. This is why bony structures aresought to be avoided in extracorporeal treatment.

Geometries presented in embodiments of the present invention can be usedwith electrohydraulic, electromagnetic, piezoelectric, or explosive orprojectile constructions in order to produce pressure shock waves.

An adjustable handle 72, as seen in FIG. 7, can be attached to pressureshock waves applicators 30, to allow an improved ease-of-use for thephysicians. A handle also keeps the physician's hands out of the X-rayfield in case a C-arm is used to monitor the procedure.

In general, cavitations produced by pressure shock waves, can generateechogenic regions that can be seen using ultrasound in B-mode. Also,contrast medium shows changes in obstructions under X-rays such as aC-arm that goes around the table where the patient is positioned duringtreatment).

The usual contrast media used for such procedures includes: gas filledliposomes, gas filled lipid bilayers, microbubbles containing liquids,gas emulsions, gas-filled micro-bubbles and micro-bubbles containingsuspensions (for example dodecafluropentone).

Any of the above mentioned contrast media can be used in conjunctionwith extracorporeal pressure shock waves devices to monitor theprogression of treatment and visualize the relative position of thedevice focal volume to the treatment area as cavitation bubblesdeveloped inside the focal volume produce hyper-echoic regions whenmonitored with fluoroscopic or ultrasound means.

This type of approach can be used for the treatment of occlusions 20that block normal flow 75 form any natural human/animal conduit/lumen.

Referring to FIGS. 8A and 8B, to increase efficiency of treatmentmultiple applicators 30, 32 (or more) can be used at the same time andcontrolled by one central console or individual consoles for eachapplicator. The choice between one console and multiple consoles isbased on the degree of coordination and complexity of the sequence ofactivation for multiple applicators for treatment.

When multiple reflectors/applicators 30 are utilized, differentauxiliary fixtures/devices 80 can be used to keep the applicators 30, 32or more in place, as seen in FIGS. 8A and 8B.

Based on the position of the blood vessels 15 or natural human/animalconduits/lumens inside the human/animal body, a set of applicators 30and 32 that contain reflectors with different geometries and angles,such as α₁ and α₂ that may have same or different values, relative tothe skin 28 may be provided to physicians to cover possible treatments.

In vascular applications directed to heavy calcifications of theocclusion cap 10 and very long vascular occlusions 20, a combination ofextracorporeal shock wave devices and suction catheter s or distalprotection catheters (introduce through the blood vessel 15) may be usedin embodiments of the invention.

As shown in FIG. 9, when the treatment is done at the proximalregion/end 33 of a vascular occlusions 20 (closer to heart), the debris95 generated by shock wave cavitation can be flushed out using acombination of catheters connected to external pumps.

Typically, before starting the extracorporeal session, a guide wire 94is introduced into vasculature through a small incision in the groin(femoral artery access) or in the arm (brachial artery approach) toallow the movement inside the vasculature of the guide catheter 92 andflush catheter 91 used to flush the debris 95 out of the treated bloodvessel 15 from the body appendage 25. Note that for a good visualizationof the end of the guide catheter 92 and flush catheter 91 inside thebody appendage 25, both catheters have radio-opaque tips 90.

The steps for the treatment in one embodiment of the invention includes:

1) Introduce guide wire 94 into vasculature and advance it until itreaches the occlusion 20.

2) Introduce over the guide wire 94 the guide catheter 92, which isadvanced using the guide wire 94 guidance until it reaches a position inthe proximal region 33 to occlusion 20.

3) Slide over the guide wire 94 and inside the guide catheter 92 a flushcatheter 91.

4) Remove the guide wire 94 and connect the flush catheter 91 to a pumpto inject saline solution inside the vessel 15.

5) Connect the guide catheter 92 to another pump that will draw themixture of blood, saline and debris 95 out of the body appendage 25.

6) Start the extracorporeal pressure shock waves device.

7) Simultaneously start both pumps that activate the flush catheter 91and guide catheter 92.

8) Continue flushing and pressure shock waves application untilocclusion 20 is penetrated.

9) Stop extracorporeal shock wave device.

10) Continue to flush for another 2 minutes.

11) Stop the pumps connected to the flush catheter 91 and guide catheter92.

12) Disconnect the flush catheter 91 and the guide catheter 92 from thepumps.

13) Remove the flush catheter 91 first.

14) Remove the guide catheter 92.

15) Close the access incision/cut from the femoral or brachial artery.

This approach may be useful for the treatment of occlusions 20 found inthe carotid arteries. The large air bubbles or debris 95 may becollected with distal protection devices for carotid arteriesinterventions. The left and right common carotids supply blood towardsthe head and branches in the neck area into internal carotids towardsthe face and external carotids towards brain. For these vessels 15 it ispreferable to not allow the flow up stream of debris 95 generated duringextracorporeal pressure shock waves treatment, which in the face areacan produce local paresis or in the brain can generate strokes. Also,devastating effects can be created by air bubbles larger than 2 mm insize flowing towards the brain (air embolism). The smaller bubbles (lessthan 2 mm in size) can be dissolved easier in the blood and can passsmall vessels as arterioles and capillaries without any problems.

Referring to FIG. 10, the treatment area can be found at differentdepths relative to the skin 28 such as with a set of treatmentapplicators 102, 104 and 106 with different penetration depths (y₁, y₂,y₃ decreasing in respective depth). A set of at least three (3)applicators 102, 104 and 106 may be provided to treat a body 27,including a variety of blood vessels 15 or normal human/animalconduits/lumens or to take into account different human/animal body mass(skinnier or fatter). In this way, treatment can occur to various bloodvessels 15 (arteries or veins) or human/animal conduits/lumens, as longas the focal volume 108 intersects the vessel 15 or human/animalconduit/lumen.

Due to inclined geometry of the reflector, in embodiments of theinvention it is desirable to equilibrate the applicator 30 from the masspoint of view and will not allow the applicator 30 to disengage thetreatment area, due to non-equilibrated mass. The consideration of massdistribution may take into account the fact that the physicians shouldkeep their hands out of the treatment regions that might be visualizedusing an X-ray device (C-arm) and thus avoiding radiation exposure. Anappropriate handle design connected to the applicator 30 body may beprovided.

Referring to FIG. 11, wheel 112 can be used to equilibrate the momentumof the applicator 30. Note that the position of the wheel 112 can beadjusted between L_(max) and L_(min) as distance away from applicator 30body.

The equations used to calculate forces for static and dynamic situationsincludes:

Governing Equation:

Total Momentum=0

Static Situation:

G _(wheel) ×x ₁ +G _(applicator) ×x ₂ =F ₁ ×x ₃ +F ₂ ×y ₃

Dynamic Situation:

G _(wheel) ×x ₁ +G _(applicator) ×x ₂ +F _(1movement) ×y ₃ =F ₁ ×x ₃ +F₂ ×y ₃ +F _(2movement) ×x ₃

In embodiments, it is beneficial if an applicator 30 can be created withadjustable angle for the internal axes to treat different blood vessels15 or natural human/animal conduits/lumens at different depth inside thehuman appendage 25 or human body generally. As shown in FIGS. 12A and12B, this approach can be realized by sitting the applicator 30 on ahinge 128 as part of an external frame 126. Note that the pivotal axis122 provided by the hinge 128 can be moved vertically in between Z₁ andZ₂. In this way penetration depth can be adjusted and the position of F₂of the focal volume 108 can be adjusted inside the treatment area (F₂ isnot shown in FIG. 12A). As shown in FIG. 12A, by rotating the applicator30 around the pivotal axis 122 a different blood vessel 16 orconduit/lumen can be treated, such as a superficial blood vessel orconduit/lumen when compared with vessel 15 or a conduit/lumen. Thisrotational movement combined with adjustable position for the pivotalaxis 122 in between Z₁ and Z₂, can give multiple treatment options tophysicians.

With continuing reference to FIG. 12B, the external frame 126 is longeron the direction of longitudinal movement 31 for the applicator 30(respectively l₁ 22 l₂) to allow the physician to correctly position ofthe applicator 30 based on intended treatment procedures. The externalframe 126 can have any possible shape. The bellows 124 (connect theframe with the applicator 30 body and keep an enclosed volume of fluidinside the applicator 30) are constructed to fit inside the externalframe 126 and for that reason shape for the external frame 126 in anembodiment is circular.

As one shown in FIGS. 8A and 8B, the whole assembly can be positioned insome embodiments in auxiliary fixtures/devices 80 to allow precisealignment of multiple applicators 30, 32.

In further embodiments, extracorporeal pressure shock waves may be usedfor treatment of stenotic plaque, vulnerable plaque, blood vessels ornormal human/animal conduits/lumen. Among plaques 130, stenotic plaqueis different from vulnerable plaque in blood vessels 15. The stenoticplaque is relatively stable and it has a thick cap that keeps theaccumulation of lipids LDL (bad cholesterol) and cellular debrisenclosed between blood vessel wall and the cap (see FIG. 13).

Stenotic plaques can reduce blood flow 39 for organs or body appendages25 (arms and legs) that translates in ischemia of the affected tissuedue to its deprivation of proper nutrients and oxygenation. Ischemictissue can be a life threatening situation if is affecting the heart(affects normal function of the heart, thus blood circulation ingeneral) or can influence limbs' extremities (can result in amputationsdue to CLI—critical limb ischemia) or can become a chronic pain in bodyappendages 25 and especially in legs (known as peripheral arterialdisease or PAD that is affecting most of the older population, withdebilitating effects for the normal life activities).

The grade of stenosis is indicated based on the percentage of crosssectional area of blood vessel 15 blocked by the stenotic plaque. Thatcan range from 5-90%, where 5% stenosis is a limited narrowing of theblood vessel 15 and 90% is a severe narrowing. The 5% up to 50% stenosisare kept under observation. After 50% blockage of the blood vessel 15cross-section, the stenotic vessels need treatment, which today is donewith angioplasty (inflate balloons inside the stenosis to dilate theblood vessel 15 and break plaque 130) or stenting (deployment of astainless steel or nitinol metallic mesh inside the stenosis to keep theblood vessel 15 opened).

The disadvantage of both stenting and angioplasty is that they producepost-procedural inflammation, which can generate proliferation of thesmooth muscle cells and consequently a re-narrowing of the vessel 15lumen (cross-section), phenomenon called restenosis. To preventrestenosis drug-eluting stents (DES) were created. These stents have themetallic scaffolding covered with polymers that contain drugs asPaclitaxel or Sirolimus, which prevent inflammation and thus caneliminate or reduce smooth muscle proliferation.

Both stenting and angioplasty procedures are minimally invasive, whichmakes them acceptable for patients with multiple comorbidities. Somecomplications with the DES can be generated by the non-epithelializationof the stents in their middle portion, which can produce late thrombusformation that can be life threatening if the stent was placed incoronary arteries (heart) or in carotid arteries.

Recently, a type of angioplasty with the balloons covered withPaclitaxel and Sirolimus was also tried to arrest smooth muscle cellsproliferation. In comparison with drug eluting stents the balloonseluting drugs represent a technology yet to be proved.

The angioplasty and stenting of stenoses, with drugs or without drugshave advantages and disadvantages as described. In embodiments, theaddition of extracorporeal pressure shock waves technology usedindependently or in conjunction with angioplasty and stenting may bebeneficial.

Vulnerable plaques (see FIG. 13) are vascular plaques that have a verythin cap that makes them prone to be easily cracked, which can let outthe mixture of cholesterol and cellulose debris from under the cap. Thespilled out mixture can generate a thrombus (can occlude arteries andthus producing tissue ischemia) or an embolus (can travel distal throughthe blood vessels 15, which can produce heart attacks for coronaries,pulmonary embolism or strokes for carotids or brain arteries). In thecase of a vulnerable plaque the crack of the cap is not dependent on thegrade of stenosis. Even 5% reduction of vessel 15 cross-sectional area(stenosis) can be life threatening in the case of vulnerable plaques.This risk associated vulnerable plaques makes such plaques a main targetfor preventive or acute treatment of stenotic vessels.

Vulnerable plaques are difficult to detect due to the fact that they areasymptomatic, until they erupt and have grave consequences. Externalmethods/technologies that may be used for detection include: MRI(Magnetic Resonance Imaging), CT (Computed Tomography); EBCT (ElectronBeam Computed Tomography), Search for inflammatory markers in blood(Interleukins 6, 18, Matrix Metalloproteinase (MMP), C-reactive protein(CRP), etc.) and Ultrasound (look for hypo echoic regions due to LDLpresence).

Internal/invasive methods/technologies are described in “VulnerablePlaques: a Brief Review of the Concept and Proposed Approaches toDiagnosis and Treatment” and “SIS ALMANAC ONLINE—Vulnerable Plaque”citations and can be categorized as follows: Intravascular Ultrasound(IVUS), Angiography, Angioscopy (direct visualization in color of thevessel wall), IVUS Elastography (combination of intravascular ultrasoundwith radio-frequency measurements), Thermography Catheters (localincrease in temp due to the presence of monophages in the vulnerableplaque), Optical Coherence Tomography, Spectroscopy (RAMAN or nearinfrared) and Intravascular MRI.

Proposed treatments for vulnerable plaques include: drug eluting stents(DES) and medication (ACE inhibitors, beta-blockers, anti-microbialagents, anti-inflammatory agents, inhibitors for MMP, etc.).

In embodiments of the invention, pressure shock waves produced in anextracorporeal manner can be used for the treatment of vulnerableplaques using the mechanisms that include: pressure shock waves toimprove endothelial function of the body, decrease the LDL (badcholesterol) levels, inhibit LDL oxidation, increase reversecholinesterase transcript, reduce inflammation and inhibit thrombosis.

Because treatments of plaque 130 such as stenotic plaques and vulnerableplaques, blood vessels' inflammations, enlarged or torturous veins(varicose veins), inflammations or degeneration of any naturalhuman/animal conduit/lumen, use the same type of construction ofequipment, the described FIGS. 14A-17 apply for both types of bloodvessels plaques 130 (stenotic and vulnerable) and for any other specifictreatment of the blood vessels 15 wall (arteries/veins) or naturalhuman/animal conduits/lumens wall.

Note that the major difference in between the treatment of blood vessels15 generally and of blood vessels 15 that have plaques 130 is thesetting for the pressure shock waves. For chronic inflammation of theblood vessels 15 wall and enlarged or torturous veins (varicose veins)the energy used is low to medium, for stenotic plaques the setting forenergy will be high and for vulnerable plaques the energy used is low tomedium (promotes tissue growth on the plaque cap). For electromagnetic,piezoelectric and electrohydraulic or projectile pressure shock wavesapplicators 30 the settings for treating vulnerable plaques will produceflux density of ≤0.2 mJ/mm² in one or more embodiments.

For stenotic plaques 130 the energy flux density should be ≥0.3 mJ/mm²to produce the elimination of the plaque in one or more embodiments.

For chronic inflammation of the blood vessels 15 or any naturalhuman/animal conduits/lumens and for enlarged and/or torturous veins(varicose veins) the energy flux density should be >0.1 mJ/mm² and ≤0.3mJ/mm² in one or more embodiments.

Also, the treatment of inflammation for blood vessels 15 or human/animalconduits/lumens, enlarged or torturous veins (varicose veins) or forvascular plaques 130 (stenotic or vulnerable) can be done independentlywith extracorporeal pressure shock waves devices or in synergy withdifferent drugs or other medical devices.

In embodiments of the invention, extracorporeal pressure shock waves arenot limited by vessel 15 or conduit or lumen size in order to treatinflammation for blood vessels 15 or human/animal conduits/lumens,enlarged or torturous veins (varicose veins), stenosis (reduce of crosssection area of blood vessels), blood clots formation in blood vessels15 (veins and arteries) or human/animal conduits/lumens. Avoiding suchlimitation is useful for blood vessels 15 where comparative angioplastyand stenting (invasive procedures) are physically limited by thecatheter dimensions (tubular devices that carry the stents inside thehuman body or have balloons at the distal end that are used to reopenthe blood vessel 15 in the stenotic area). Thus angioplasty and stentingcannot be done for vessels 15 smaller than 2 mm in diameter size.

Referring to FIG. 14A, for the treatment of any type of plaques 130(stenotic or vulnerable) or blockages of the arteries, veins, naturalhuman/animal conduits/lumens due to blood clots (thrombus or embolus),the focus of the pressure shock waves should be done on the vessel 15 orconduit/lumen wall in front of the targeted area and as perpendicularpossible to the vessel 15 or conduit/lumen wall.

When there is no patient risk in generating debris 95 down the flowstream 39 inside a blood vessel 15 or a natural conduit/lumen (forexample blood vessels of the limbs present lower risk of debris 95blocking small vessels compared with neck, brain, or heart vessels),applicator 30 can be focused on plaque 130 or in front of the plaque 130as shown in FIG. 14B. In one illustrated embodiment, a 90° angle isprovided in between the direction of the applicator 30 and vessel 15 orconduit/lumen walls. Also, a long focal volume 108 can cover the wholevessel 15 or conduit/lumen cross-sections, which can give action fromcavitation and/or by the compressive forces both on the surface of theplaques 130 and on the lipids trapped inside the plaques 130. As shownin FIGS. 14A and 14B, a variable penetration is helpful to applytreatment correctly, particularly for big vessels 15 or natural conduitsor lumens (large diameter) or for the vessels 15 or conduits/lumens thatchange penetration relative to the skin 28 on their path inside anappendage 25 or body generally.

The approach presented in FIGS. 14A and 14B can be used to eliminateblood vessels 15 or natural human/animal conduits/lumens spasm(especially when catheters, guide wires 94, stents, balloons, or otherinvasive medical devices, etc. are used to navigate through vessels 15or conduits/lumens or stretch them). A similar approach can be alsoapplied to reduce the chronic inflammation of the blood vessels 15 andother natural conduits/lumens of the human/animal bodies, which can havedebilitating effects in the long term.

Referring to FIGS. 15A and 15B, in order to cover the entire stenoticregion, applicator 30 can have longitudinal movement 31 combined withtransversal movement 142. For arteries that can pose the risk for theblood flow 39 carrying debris 95 (plaque fragments, blood clots, etc.)from the stenotic area in sensitive areas (brain or heart) the pressureshock waves may be delivered with the use of distal protection devices(such as baskets 35 or occlusion balloons 154).

The distal protection system preferably is able to pass the plaques 130(stenotic or vulnerable) towards the distal region 34 of the plaque 130,to protect the smaller vessels down the flow 39 to be blocked by debris95 (not shown in FIGS. 15A and 15B) and/or embolus from the plaques 130and thus seeking to prevent tissue ischemia (lack of oxygen andnutrients).

For distal protection, either basket devices 35 (see FIG. 15A) orballoon occlusion 154 devices (see FIG. 15B) can be used. The maindifference is that the baskets 35 have a mesh with pores ≥10 μm thatcollect debris 95 larger than 10 μm and in the same time allow thenormal blood flow 39 to take place. The balloon occlusion 154 devicesuse guide wires 94 with balloons on their distal end. The balloon guidewire 94 is positioned to allow the inflation of the occlusion balloon154 after stenotic area. In this way the debris 95 are collected aroundthe proximal surface of the balloon. This solution completely blocks theblood flow 39 during procedure. The collected debris 95 can be extractedusing:

Passive extraction as presented in FIG. 15B. Practically, a suctioncatheter 93 is positioned in such way to allow the suction of bloodcolumn with collected debris 95. The suction is created by connectingthe proximal end of the suction catheter 93 to a syringe.

Active extraction as presented in FIG. 9. In this case the collecteddebris 95 around the proximal end of the occlusion balloon 154 isstirred by the active flush produced by the flush catheter 91 andcollected by the guide catheter 92, which thus has a dual role—to guidethe flush catheter 91 inside the vasculature and also to collect throughactive suction the debris 95. In this case dedicated pumps need to beused to drive the flush catheter 91 and the guide catheter 92.

The disadvantage of the catheter system that uses the occlusion balloon154 is given by the complete blockage of blood flow 39 during action,which can be restrictive, especially for the treatment of carotids orheart arteries.

In an embodiment for visualization inside the human body, the suctioncatheter 93 from FIG. 15B has radio-opaque markers 152 that can be seenusing fluoroscopy, which helps with the correct positioning of thesedevices inside the blood vessels 15 or natural conduits/lumens 17. Theocclusion balloon 154 from both FIGS. 15A and 15B are filled withcontrast agent that makes them visible under fluoroscopy.

Sometimes is desired that a totally enclosed space be created in thetreatment area from a body appendage 25 or body, as shown in FIGS. 16Aand 16B. This closure can be accomplished with the use of an occlusioncatheter 96 that uses two balloons—first balloon 154 in the proximalregion 33 to the plaques 130 (stenotic or vulnerable) or targeted area145 and the second balloon 156 in the distal region 34 to the plaque130, 135 or targeted area.

The newly created space can be emptied from blood (in case of bloodvessels 15) or any other body fluid (for natural conduits/lumens) andmedical saline solution can be introduced. This saline solution shouldbe able to create much faster cavitation bubbles than the blood or anyother body fluid, which can facilitate the cavitation action of thepressure shock waves inside the focal volume 108. After the shock wavetreatment, the occlusion balloon 154 will be deflated letting the bloodflow 39 or body fluid normal flow 75 to get in the protected space andfinally the occlusion balloon 156 is deflated and the occlusion catheter96 can be retrieved over the guide wire 94. As can be seen from FIG.16A, before deflation of the occlusion balloon 156 a passive suction viasuction holes 164 (using a medical syringe attached to the occlusioncatheter 96) can be applied to collect any debris 95 (not shown in FIGS.16A and 16B) trapped proximal to the balloon 156.

In some cases besides the saline solution, drugs in liquid form can alsobe added in the occluded space via drug delivery holes 166 (see FIG.16B), which can help with plaque 130 (stenotic or vulnerable) and/orblood clots (thrombus or embolus) elimination or for any treatment ofthe blood vessel 15 wall or natural human/animal conduit/lumen wall thatrequired specific high dosage medication that is not recommended to beadministered systemically. The advantage of delivering a highconcentration substances added in the saline solution is that will havea high probability of affecting vessel 15 walls (including plaques 130)or natural human/animal conduit/lumen wall from the targeted area 145and in a synergetic effect with the pressure shock waves. For example,the pressure shock waves can open micro-cracks in the plaques 130 orblood vessels 15 walls or conduit/lumen walls and thus allowing thepenetration of substances/drugs inside the plaque 130 or vessel 15 wallsor conduit/lumen walls.

For removal/dissolution of the blood clots from veins usingextracorporeal pressure shock waves, as sole treatment or in combinationwith specific drugs, the big advantage is given by the fact that thepressure shock waves treatment can be done without affecting the valvespresent in veins.

Substances/drugs that can be added in the saline solution innon-limiting below, although embodiments include: heparin, tacrolimus,beta blockers, paclytaxel, thrombolitic substances, ACE inhibitors,cyclosporin, antibiotics, antimicrobial agents, sirolimus,anti-inflammatory drugs, other tissue growth inhibitors and the like.

The use of pressure shock waves alone or with drugs in an enclosed spacethat contains the stenotic regions or targeted treatment area isapplicable to the embodiments presented in FIGS. 16A and 16B.

Furthermore, the pressure shock waves can be used to reducepost-procedural inflammation after angioplasty (balloons inflated insidethe stenotic region) or stenting of a blood vessel 15 or any naturalconduit/lumen.

Referring to FIG. 17, stents 170 are open structures that allow pressureshock waves to travel through them. Due to the nature of the stents 170(metallic or plastic meshes) there will be interference between pressureshock waves and stents 170, which will affect the focusing of thepressure shock waves and finally their efficiency. For treatment oftissue from a blood vessel 15 or a natural human/animal conduit/lumeninside a body appendage 25 or body generally with the stents 170incorporated therein, the focus is preferably on the soft tissue aroundthe stent 170. In some embodiments, an applicator 30 with a very largefocal volume 108 (FIG. 17) is used.

When compared with stenotic plaques, vulnerable plaques 135 may betreated with similar approaches, with the distinction that low energysettings will be used (low spark discharge voltages or energy actuationfor electromagnetic, piezoelectric or projectile devices) combined withlower number of shocks (minimum 100, and maximum 1500). The sameprinciples apply for the treatment of a stent in a targeted area 145 ofa natural human/animal conduit/lumen. Also, the focus of the pressureshock waves should be on blood vessel 15 walls or conduit/lumen walls.Where no debris 95 is generated by the process in one or moreembodiments, the distal protection is not necessary. The treatment canbe done in one enclosed space, with pressure shock waves only (see FIG.16A), or with addition of drugs (see FIG. 16B). The synergetic effectbetween highly compressive waves and cavitation that push the drugsinside the tissue (due to cavitation microjets) can help to thicken thecap of the vulnerable plaques and thus preventing their rupture.

An advantage of extracorporeal pressure shock waves usage in treatmentof blood vessels 15 or natural human/animal conduits/lumens is that itcan be performed without any major inconvenience to the patient. Thetreatments can be administered in one or more sessions and at differentor equal time intervals. If restenosis occurs, the shock wave treatmentcan be applied immediately without any kind of surgery or invasiveprocedure in various embodiments.

Based on their efficacy, pressure shock waves delivered extracorporeallycan also be used as prophylactic treatments, such as to prevent plaque130 (stenotic or vulnerable) formation for patients genetically prone todevelop vascular disease. The time intervals can be from 1 day to 30days or more. A combination of pressure shock waves deliveredextracorporeally with invasive means (catheters, guide wires 94) can bemore complicated for the patient. In any case, if the pressure shockwaves can enhance drug delivery or help to achieve the targeted goal, itis still beneficial to the patient. Introduction of guide wires 94,guide catheters 92, diagnostic catheters, flush catheters 91, inside thevasculature (via femoral or brachial access) represent minimal invasiveprocedures that are practiced conventionally. Furthermore, for naturalhuman or animal conduits or lumens the use of any invasive means inconjunction with extracorporeal pressure shock waves is even lesscomplicated when compared with the blood vessels 15. In general, if ametallic structure (stent 170, guide wires 94, catheters made ofmetallic hypo tubes, etc.) is present in the focal volume 108 of theshock wave devices, the structure will be an interference, which usuallymoves the focal point F2 proximal to the structures. This phenomenon maybe used to move F2 from inside the vessels 15 or conduits/lumens totheir wall.

Extracorporeal treatment may also be used to treat shunts/fistulasbetween an artery and a vein using harvested vessels, grafts and/orstents, and for thrombus/embolus elimination from blood vessels ornatural human/animal conduits/lumens. In general, when a slow blood flow39 occurs in the vasculature due to occlusions 20 or stenosis, there isan increased chance of thrombosis. Also, when foreign objects areflowing or sitting in the vasculature, the body reaction is to clotblood around them using the thrombosis mechanism. As shown in FIG. 18,in cases where an artificial material is used to create an alternativeconduit for the blood flow 39 using artificial vessels 184 or graftsmade of DRACON, PTFE, etc., thrombosis may occur too. The thrombosisrisk is elevated with shunts (fistulas), which are created between anartery 180 and a vein 182 in a compromised vasculature due tohemodialysis, for example. Through shunts the blood can slowly move fromthe arteries 180 to the veins 182. Due to big difference in velocitybetween the blood flow 39 in the arteries 180 and the veins 182 (veryslow in veins 182 compared to arteries 180) vortexes are created anddead spaces, which can entrap blood and thus creating blood clots proneareas 185, as can be seen from FIG. 18. Furthermore, due to slow movingblood and due to the contact with a foreign substance/material, thedistal area of the shunts represents the perfect environment to createadditional blood clots prone areas 185.

In these cases, stents 170 might be used to open the shunt (not shown inFIG. 18).

Even in the presence of the stents 170 inside the shunts, there arezones where blood clots prone areas 185 are formed in the metallic meshof the stent 170 due to the same big difference in velocity between theblood in the arteries 180 and the veins 182 and the presence of foreignmaterial of the stent 170. The blood clots from the stents 170 can growin size and thus blocking the shunt (artificial vessel 184).

Blood clots (thrombus or embolus) can also be created during theinjury/trauma of a vessel 15 or of a natural human/animal conduit/lumenor in the case of rupture of the cap of plaques 130. To repair therupture/trauma the organism brings clotting agents that promote theformation of a blood clot (thrombus) that can grow in size to asufficient dimension to block the active blood circulation 39 from bloodvessels 15 or the normal fluid flow from natural conduit/lumen or cantravel through the vessel 15 or conduit/lumen in the form of embolusuntil it reaches a smaller diametric dimension of the vessel 15 orconduit/lumen, where it produces a blockage.

To eliminate blood clots from natural blood vessels 15 (arteries 180 andveins 182) or artificial vessels 184 (shunts or bypass harvestedvessels) or from natural human/animal conduits/lumens the pressure shockwaves generated externally (extracorporeal) can be used to break thiscoagulated blood (lysis of the blood). The pressure shock waves can beused alone or in combination with thrombolytic drugs. For blood clotsformed inside natural vessels 15 or natural human/animal conduits/lumensany approach as presented in FIGS. 14A, 14B, 15A, 15B, 16A, 16B or 17might be used.

The extracorporeal treatment using pressure shock waves for blood clotsformed in shunts or bypasses using artificial vessels 184 ornatural/harvested vessels 15 is possible due to the fact that in thesecases the shunts made of artificial vessels 184 or natural/harvestedvessels 15 are placed immediately under or closer to the skin 28.

For blood clots formed in shunts or bypass artificial vessels 184,reflectors 22 with elliptical geometries can be used that producesuperficial penetration (10 to 30 mm), reflectors that have the semiaxis ratio of b/c≥1.1 and b/c≤1.6 . Spherical or parabolic (y²=2 px)reflectors 22 can be also used due to the superficial treatmentnecessary for these situations.

The detailed treatment choices for shunts are identical in embodimentsof the invention to those presented on FIGS. 14A, 14B, 15A, 15B, 16A,16B or 17.

Extracorporeal pressure shock waves may also be used for the treatmentof in-stent restenosis. After stenting of stenotic regions, there is arelatively high potential that the tissue will grow back through thestent 170 and produce a new stenotic region that can reduce the bloodflow 39 from a blood vessel 15 or the normal fluid flow from a naturalhuman/animal conduit/lumen. This phenomenon is called in-stent (insidethe stent 170) restenosis 190, as shown in FIG. 19. This new stenoticregion that incorporates a stent 170 underneath it is very difficult totreat, due to the reduced vessel 15 or conduit/lumen 17 diameters.Sometimes for blood vessels stents 170 angioplasty balloons are used topush the new formed tissue and the stent 170 radially away from the axisof the vessel 15 or conduit/lumen. Although this approach can besuccessful in short term, it does not offer a preferable long-termsolution. For blood vessels 15 used with drug eluting stents (DES)in-stent restenosis 190 is often reduced when compared to bare metalstents 170.

The use of non-invasive (extracorporeal) pressure shock waves mayprovide a solution for in-stent restenosis. The inflammation and tissueproliferation may be arrested immediately after the stenting procedureusing the approach presented in FIG. 17 to reduce post proceduralinflammation, smooth muscle growth and finally in-stent restenosis 190.If the in-stent restenosis 190 was produced, then the pressure shockwaves can be used to treat this chronic condition, as shown in FIG. 19.

The pressure shock waves are delivered in embodiments in the stenoticarea developed inside the stent 170. The focal point F₂ of the focalvolume 108, where the pressure shock waves are concentrated, should beinside the stenotic plaque 130 of a blood vessel 15 or targeted area ofa natural conduit/lumen. Minimal interference with the metallic mesh ofthe stent 170 may be provided. If the pressure shock waves pass throughthe stent 170 (highly possible) then consideration might be given to theshift of the F₂ away from the stent 170.

Depending on the type of vessel 15 or conduit/lumen treated and itsposition inside the body or body appendage 25, this procedure will beimplemented distal protection to capture debris 95 generated duringprocedure, as presented in FIGS. 15A and 15B. Also, an enclosedtreatment space approach can be used (especially for combination ofpressure shock waves and drugs), as shown in FIGS. 16A and 16B.

In further embodiments, extracorporeal pressure shock waves can be usedto treat the heart in non-limiting examples such as: treatment ofmuscles that activates the heart valves to strengthen them, eliminateany excess pericardial fluid accumulation from the pericardial cavity(pathologic, accidents or due to heart surgical intervention); treatischemic muscle that resulted after a myocardial infarction episode;revascularization of heart muscle, 2-3 weeks before stem cells genes orgrowth factors applications (injection) in the ischemic tissue thatresulted after a myocardial infection; adjunct treatment duringinjection of stem cells, genes or growth factors into tissue; in generalfor tissue regeneration and in particular for myocardial infarctionischemic tissue, auxiliary treatment post injection of stem cells, genesor growth factors into tissue; in general for tissue regeneration andrevascularization, and in particular for myocardial infarction ischemictissue regeneration; and treatment for destroying internalfibrotic/scarring tissue and regrowth of viable heart muscle andtreatment after heart surgery or coronary interventions to enhancehealing.

Challenges of treating the heart tissue, pericardium and pericardialcavity using pressure shock waves (extracorporeal) include factors suchas: chest ribs bone in front of the pressure shock waves (they obstructthe penetration of pressure shock waves towards heart); the presence ofthe lungs behind the heart can interfere with the treatment of theposterior tissue of the heart; pressure shock waves change dramaticallytheir speed at the boundaries where the sound speed changes (soft tissueto air) and in this way can produce lung hemorrhagic lesions; and breasttissue in front of the heart can also produce variable penetrationdepth.

To avoid the interference of the bony structure of the rib cage,reflectors 200 as shown in FIG. 20 may be small in size to be placed inbetween the ribs, with an aperture (a) that allows pressure shock wavesto focus in F₂ and with a diameter of the focal volume 108 of the orderof 1-2 cm or less.

With continuing reference to FIG. 20, the effective treatment of theheart 209 muscle can be accomplished by designing special heartapplicators 200 with small elongated apertures to match the openingsbetween ribs 208 and with deep reflectors to allow the necessarypenetration to reach the heart 209 tissue, when heart applicators 200are maintained in contact with the patient chest 207.

The dimension of the reflector largest diameter Φ is 10-40 mm, whichproduces a mini-reflector. Due to its reduced dimension the discharge inF₁, in embodiments the voltage applied for electromagnetic orpiezoelectric approach is reduced to 1-14 kV or even lower. To overcomethe reduction in energy delivered with each shock, one embodiment uses80-90% of the ellipsoid (increased reflective area surface), comparedwith classic approach where only 50% of the ellipsoid surface is used tofocus the pressure shock waves.

The use of 80-90% of the ellipsoid surface is done by combining a lowershell 202 with a distinctive upper shell 204, which together form mostof the internal surface of the ellipsoid. This embodiment provides amuch higher efficiency in shock transmission and focusing. The topportion of the heart applicator 200 has a membrane 205 on top of a smallaperture (a) of 5-10 mm that is constructed to fit the intervertebraeopenings and concentrates the reflected waves towards the focal volume108 without interference.

Minimal interference is preferable in points A and B to allow distortionof the signal between compression and tensile phase. That can berealized through a small difference in size of the connection betweenupper shell 204 and the lower shell 202.

An elongated applicator 210, shown in FIGS. 21A and 21B, can increaseefficiency of the treatment and the triggering of the pressure shockwaves in multiple Fi (discharge points 68), which can be done in thesame time or sequential using a shock wave generator 60 based on theneeds of the treatment. The cross section of the reflecting surface 215of the special elongated applicator 210 can be an ellipse (as presentedin FIG. 21A) or can be a parabola, a circle or any combination of thesegeometries. The actuation/control of the special elongated applicator210 can be done using the actuation button 217. The reflecting surface215 can be also created using piezoelectric elements as crystals, thinfilms or fibers. Finally, the aperture area covered by the membrane 205is preferably comparable with intervertebral openings to avoidinterference of the pressure shock waves with rib cage bones.

A reflector with angled geometries is shown in the embodiment of FIG. 22as a multi-reflectors' applicator 220. To create this applicatorembodiment, three pieces (first reflector portion 222, second reflectorportion 224 and top piece 225) are assembled together to achieve theillustrated enclosed space used to focus pressure shock waves confocalin the treatment area. The focal volumes (first reflector focal volume221 and second reflector focal volume 223) have controlled length toavoid penetrating inside the heart chambers. Also, the aperture areacovered by the membrane 205 is preferably comparable with theintervertebral openings, as described with reference to FIGS. 20, 21Aand 21B.

A reversed reflector 230 for cardio application is illustrated in FIGS.23A and 23B. The geometry of the reversed reflector 230 is created inembodiments by slicing an ellipsoid longitudinally and not transversalas it was done with the classic approach for a reflector geometry.Reversed reflectors 230 are able to generate radial waves 235 andfocused waves that are directed in focal volume 237, acting insequential manner on the treatment area. Such design can increasetreatment efficiency. Contact with the body 27 occurs via membrane 205covering the aperture 232 of the reversed reflector 230. As describedwith reference to FIGS. 20, 21A and 21B, the aperture 232 preferablymatches the distance in between ribs 208, for an efficient treatment ofthe heart 209 using extracorporeal pressure shock waves.

The shape, b/c ratio, and inclination of applicators (any of applicators200 or 210 or 220 or 230) that treat extracorporeal the heart 209 andpericardium will dictate penetration and how it will be used, as shownin FIGS. 24A and 24B. In the depicted embodiments, it is easier to treatthe anterior aspect of the heart 209, pericardium and pericardialcavity, via the contact with chest 207.

It is typically more difficult to treat the posterior part of the heart209, pericardium and pericardial cavity (against the left lung 242). Inposterior treatment tangential pressure shock waves may be used(tangential pathway relatively to the heart 209 muscle instead ofperpendicular as can be used for the treatment for the front part of theheart 209).

Another approach to treat the posterior part of the heart 209 is to haveextracorporeal pressure shock waves transmitted through the heart 209chambers from the chest 207 area and precisely focus them only on theposterior part of the heart 209. In general, the penetration of thepressure shock waves in lungs (left lung 242 and the right lung 244) arepreferably avoided and including avoiding application of extracorporealpressure shock waves to the back 206 of the body 27.

Extracorporeal pressure shock waves may also be used for pacemakersleads, implants and prostheses extraction. Pacemakers are devices usedto deliver mini-electric shocks to the heart muscle when the naturaltriggering mechanism of the heart 209 gets irregular (erratic).Pacemakers can identify arrhythmias and eliminate them. Pacemakers haveleads that are implanted deep into the heart muscle and the deviceitself sits subcutaneously. A pacemaker's battery has a limited life upto 10-15 years of functioning. This lifespan is why pacemakers need tobe replaced after a long period of time. The leads attached inside theheart have tissue growth around them that sometimes makes theirextraction difficult. This growth can lead to injury of the heart muscledue to extraction of tissue together with the leads. To minimize tissueinjury, facilitate implantation of a new device without complications,pressure shock waves may be used to loosen the leads before extraction.

As shown in FIG. 25, when pressure shock waves travel through theseparation of substances with the same acoustic impedance 250 (forexample water to tissue), the waves are transmitted without any losses(transmitted wave without losses 251). When there is a change ofacoustic impedance from one substance to another 252 (tissue to metal ormetal to tissue for example) a part of the waves is reflected (reflectedwave on the entry surface 253) and another part is transmitted throughthe hard metal (transmitted wave with losses 254) and then bounce backat the back surface (reflected wave on the back surface 255). Only asmall percentage is transmitted afterwards in the adjacent tissue(transmitted wave at the exit surface into adjacent tissue 256).

Based on multiple reflections on the surface of the metal lead andinside its structure, shock waves may be used to help to dislodge theleads of the pacemaker 268 from the surrounding tissue, as shown in FIG.26.

Extracorporeal angled reflectors (reflector 261 and reflector 262) incontact with the skin 28 of the chest 207 are used in the depictedembodiment. Applicator 261 has its focal volume 265 intersecting one ofthe leads of the pacemaker 268 and second applicator 262 has its focalvolume 266 intersecting the other electrode of the pacemaker 268. Thetriggering of the pressure shock waves preferably occur in accordancewith heart beats to generate pressure shock waves during “R” position ofthe curve representing the peak amplitude during a heart contraction.This triggering is preferable for any pressure shock waves that areapplied to the heart 209.

The “loosening” principle utilizing shock waves can also be applied forloosening orthopedic prosthesis from bones (hip or knee replacements) orfor removal of any implant from the human body 27 that was encapsulatedby the tissue during its service.

If a movable discharge is used (variable voltage discharge on F₁F₂ axisfor the electrohydraulic devices) then a moveable focal volume 108 canbe achieved, which gives treatment flexibility. This concept will bepresented in detail later on in this document.

Use of extracorporeal pressure shock waves may also be used forcellulite, body sculpting, skin rejuvenation, “spider veins”, burns,acute and chronic wounds, scar tissue, lymph-edema and enhancement ofcollateral blood flow. Pressure shock waves can be used to liquefy fat(adipose tissue), which then can be pushed together with cellular debrisinto lymphatic system due to the pressure gradient created by thepressure shock waves.

Also, pressure shock waves can create new collagen structures orreinforce the existing ones through cellular interaction and expression.Stronger collagen structures translate into stronger and more flexibleskin 28.

Furthermore pressure shock waves can produce angiogenesis of small bloodvessels (as arterioles and capillaries) that can enhance the bloodcirculation and stimulate cellular repair in the treated area or allow abetter flow of blood towards and from body extremities. This can enhancethe overall cosmetic and healthy aspect of the skin 28. For producingenhanced blood circulation in the limbs multiple reflectors or elongatedreflectors with multiple points of origin for the pressure shock wavescan be incorporated in “braces-like” or “boots-like” constructions thatcan make the treatment user and patient friendly. Multiple reflectorapplicators 220 or elongated applicators 210 with multiple points oforigin for the pressure shock waves (discharge points 68), which can beused for such constructions, are presented in embodiments shown in FIGS.21A, 21B, 22, 63, 64A, 64B, 65A, 65B, 65C, 66A and 66B.

Pressure shock waves may be used to activate factors involved in woundrepair (acute and chronic wounds including burns) such as VEGF (VesselEndothelial Growth Factor), TGF β (Transforming Growth Factor β), EGF(Epidermal Growth Factor), FGF (Fibroblast Growth Factor), vWF (vonWillenbrand Factor), TNFα (Tumor Necrosis Factor a), PDGF (PlateletDerived Growth Factor), HIF (Hypoxia-Inductive Factor), and the like.The calling of the body repair mechanism through the stimulation of theabove mentioned factors combined with angiogenesis (formation of newsmall blood vessels from pre-existing ones) and vasculogenesis(formation of new small blood vessels) can create the optimalenvironment for healing. The angiogenesis and vasculogenesis may createnew blood vessels that can enhance the amount of blood that is broughtinto the treatment area, which provides increased oxygenation of thetissue and brings more nutrients in the area, two critical components tosustain the healing mechanism.

Pressure shock waves can also be used to break down scar tissue andreplace with healthy tissue, improving the cosmetic aspect of the skin28.

Extracorporeal pressure shock waves can also be used to reinforce thewall of the small veins and push stagnant blood from them to reduce theso called “spider veins” aspects of the skin 28 produced by poor venouscirculation.

Based on such various embodiments, pressure shock waves can be used toreinforce the skin 28 (a collagen based structure), rejuvenate it,improve its cosmetic presentation, heal its acute and chronic wounds orto reduce or eliminate the fatty deposits from under the dermis and thusreducing the bumpy skin aspect of the cellulite or to produce bodysculpting.

Because cellular debris can be pushed in the lymphatic system bypressure shock waves and because of possible repair of the lymphaticvessels by pressure shock waves, another application for extracorporealpressure shock waves is treatment of lymph-edema, which is anaccumulation of lymph in the body extremities/appendages 25 thatproduces deformities of the limbs and mobility issues.

The pressure shock waves devices can be used as sole treatment or inconjunction/synergy with other medical devices to treat theabove-mentioned conditions or enhance the outcome of the treatment.

The treatment area for various conditions can be found at differentdepths relative to the skin 28. Exemplary penetration depth of pressureshock waves for cellulite, skin rejuvenation, wound healing, scars and“spider veins” is only superficial in the order of 1-30 mm. Exemplarypenetration depth for lymph-edema, improved collateral blood circulationand body sculpting can be up to 100 mm. The penetration depth willdictate the depth of the reflector shape, which can be shallow forsuperficial applications or very deep for applications where the focusis done deep inside the human body 27.

In order to create flexibility regarding the depth penetration during atreatment, embodiments shown in FIGS. 27A and 27B can be used. Withvarying depth, the treatment can be applied to different subcutaneoustissue layers 272 of the human/animal body 27 as long as the focalvolume 108 intersects the desired treatment site. Depending on thequantity and position of fat accumulated under the skin 28, thereflector embodiments presented in FIGS. 27A and 27B may be used forpossible cosmetic applications (cellulite, extracorporeal bodysculpting, scars, lymph-edema, etc) or for wound healing.

The rotation of the applicator 30 around the pivoting axis 122 allowsprecise positioning of the focal volume 108 inside the treatment areabased on its position relative to the skin 28, the normal curvature ofthe human body 27 and the shape/thickness of the cushion/gel pad 52.

External frame 126 is longer on the direction of longitudinal movement31 for the applicator 30 to allow the physician to correctly position ofthe applicator 30 based on intended treatment procedures. External frame126 can have many possible shapes. The bellows 124 are constructed tofit inside the external frame 126 and for that reason one preferredshape for the external frame 126 might be circular, which is differentfrom embodiments shown in FIGS. 27A and 27B.

Also, the same embodiments presented in FIGS. 27A and 27B can use thebellows 124 as a sealed chamber from which a vacuum suction 275 can beapplied, to enhance the pressure shock waves treatment with a mechanicalstimulation by pulling the skin 28 and adjacent tissue layers 272(including the fat layer) upwards using a pressure from 100 mbar up to1000 mbar. Pressure shock waves and the mechanical stimulation shouldwork in synergy to increase efficiency of the treatment. Both pressureshock waves and mechanical stimulation are known to produce formation ofnew collagen fibers into the dermis and enhances localized bloodcirculation both in dermis/skin 28 and adjacent tissue layers 272, whichshould enhanced the skin 28 firmness and overall cosmetic aspect.

In the case of wound healing, vacuum suction 275 can be used to extractany exudates out of the wound bed before starting the application ofpressure shock waves.

Inclined geometry of the reflector may increase flexibility of thetreatment, to equilibrate the applicator 30 from the mass point of viewand will not allow the applicator 30 to disengage the treatment area.Mass distribution may account for physicians that should keep theirhands out of the treatment regions that might be visualized using acamera, to track treatment progress via sensors.

As shown in FIG. 28, a roller 282 can be used to equilibrate themomentum produced by the applicator 30 handle. If necessary, theposition of the roller 282 can be adjusted to produce more flexibilityfor the treatment.

This approach can be used in embodiments for cellulite treatment, skinrejuvenation, scars or body sculpting to allow the easy use of theapplicator 30 and coordinate the pressure shock waves with a mechanicalmassage produce by the roller 282, which can enhance the effects of thepressure shock waves in formation of new collagen fibers, in pushing ofliquefied fat into lymphatic system and in enhancing the local bloodcirculation.

Another embodiment with a combination devices that can use pressureshock waves connected with mechanical double stimulation via vacuumsuction 275 and rollers 282 movement is shown in FIG. 29. A reflector isincorporated in this applicator 30 with the focal volume 108 able tointersect sufficient thickness of the treatment area (skin 28 and thefat layer 293 of the body 27), to be sure that the pressure shock wavesaccomplish their role. Simultaneously, the mechanical stimulation isgiven to the “rolled and vacuum suction affected tissue” 292. The focalvolume 108 positioning during treatment, is preferably considered inview of the raise of the “rolled and vacuum suction affected tissue”292, which is influencing the intersection of the focal volume with thetargeted/treated tissue. The transmission of the pressure shock waves tothe tissue occurs via a cushion/gel pad 52 or liquid sack present inbetween the rollers 282.

Extracorporeal pressure shock waves may further be used for controlledfragmentation of biodegradable stents. In order to allow multipletreatments of the stenotic areas of a vessel 15 (reduction in vesseldiameter due to stenotic plaque 130 build-up), a new trend in cardiologyis to use biodegradable stents that may be loaded with drugs to block orarrest smooth muscle growth. The advantage of the biodegradable stentsis that they can keep the blood vessels 15 open for a sufficient time toallow stenotic plaque breakages and healing, and after that they areabsorbed by the body 27 in a period ranging from three months to oneyear or even more. By disappearing through biodegrading process from thetissue or blood vessel 15 wall in time, biodegradable stents do notleave behind any structure incorporated into the tissue and a newtreatment can be applied with a new stent without having on overlap andbuild-up of foreign structures in the blood vessel 15 wall, as is thecase with metallic stents 170.

The difficulties with biodegradable stents include: reduced radialstrength of the biodegradable stents when compared with metallic stents170 translates in less efficacy in treating strong stenosis; the erratic(uncontrolled) degradation of the biodegradable stents might startbefore total incorporation in the blood vessel 15 wall and thus largeparts of the stents can flow down the blood stream 39 and can triggerthrombolytic events, that can then produce cardiovascular problems andeven death for the patient; and sometimes the design of thebiodegradable stents do not permit total incorporation in the bloodvessel 15 wall, which makes these stents prone to let parts of themflowing down the blood stream/flow 39, which can generate cardiovascularproblems and even death for the patient, due to the blockage of theblood vessel 15.

To address reduced radial strength of the biodegradable stents,different geometries are proposed by the industry: mechanical interlockswhen stents are deployed to their maximal dimensions, increasing thethickness of the stent struts and using stronger materials (combinationof biodegradable polymers as poly-L-lactide, polyglycolic acid (PGA),high molecular weight poly-L-lactic acid (PLLA), poly (D,L-lactide/glycolide) copolymer (PDLA), and polycaprolactone (PCL), withmetallic biodegradable materials as magnesium alloys).

FIG. 30A presents an embodiment for a biodegradable stent 300 with aknitted pattern or zigzag helical coil for the circumferential design303 to contact with the vessel 15 wall. The circumferential design 303is combined with a stent luminal radial reinforcement 305 with twoperpendicular and foldable walls inside the biodegradable stent 300, asshown in FIG. 30B.

The perpendicular walls run the length inside the biodegradable stent300 as they are dimensioned in such way to produce reinforcement inradial strength and in the same time to allow a normal blood flow 39through the biodegradable stent 300.

The challenge of embodiments similar to the one presented in FIGS. 30Aand 30B includes not all the scaffolding of the biodegradable stent 300can be incorporated into the blood vessel 15 wall, which duringdegradation of the biodegradable stent 300 can produce large pieces thathave eventual potential of producing blockage down the blood flow 39.For these situations, the degradation of the biodegradable stent 300 canbe controlled using pressure shock waves to break at a given timeframeinto small particles that cannot produce blockages and can be easilydegraded by the body 27 afterwards (see FIG. 31).

By using pressure shock waves to break such biodegradable stent 300structures after a given timeframe, the patient is provided abiodegradable stent 300 has accomplished its role (push the plaque 130against the blood vessel 15 wall) and can be safely disintegratedwithout creating hazardous situations. To cover the whole area of thebiodegradable stent 300 during extracorporeal pressure shock wavetreatment, the applicator 30 (in contact with the skin 28) can have alongitudinal movement 31 that can be combined with transversal movement142.

In embodiments to collect the fragments of the biodegradable stent 300floating inside the blood vessels 15, distal protection systems can beused. The distal protection systems utilize debris collection baskets 35or flush catheters 91 combined with suction catheters 93 or occlusionballoon 154 or occlusion catheters 96, which can be concomitantly usedwith extracorporeal pressure shock waves treatment, as shown in FIGS.15A, 15B, 16A and 16B.

Extracorporeal pressure shock waves can be used in embodiments of theinvention for controlled drug delivery. Efficient intracorporeal orpercutaneous drug delivery is very important for localized treatment ofdifferent diseases. This approach is preferred by many patients whencompared with systemic drug delivery, which has reduced efficiency andhigh probability of side effects.

Local delivery of a drug typically uses high doses that can be veryeffective without creating a systemic reaction to the increased dose orwithout losing high efficacy by delivering the drug through digestivesystem (systemic delivery). Also, in some cases it is desired to avoidthe sanguine system delivery of a drug, to avoid affecting organs andtissues that are not targeted for the treatment.

Local drug delivery can be done via patches or biodegradablepouches/structures/patches incorporated inside the targeted tissue via apercutaneous approach. Biodegradable pouches/structures/patches 320 usedfor high efficiency drug delivery can include the embodiments depictedin FIGS. 32A and 32B.

The drug delivery system presented in FIGS. 32A and 32B is capable ofdelivering two different drugs (drug 321 and drug 322) and it presentsitself as a thin biodegradable foil that has ellipsoidal pouches filledwith drugs (321 or 322) at high concentration. The pouches are createdusing thin biodegradable films/thin foil and the drugs (321 or 322) arein a fluid form to allow the cavitation formation during extracorporealpressure shock waves treatment. To perforate the pouches and thusreleasing the drugs (321 or 322) into the tissue, the main mechanism isthe collapse of the cavitation bubbles generated by the pressure shockwaves in the focal volume 108. Cavitation bubbles collapse produces highvelocity micro-jets, which can puncture the pouches and thus slowlyreleasing the drugs (321 or 322) in the treatment targeted tissue.

In order to be successful in releasing drugs 321 or 322 usingextracorporeal pressure shock waves it is very important that theextracorporeal shock wave applicator 30 positioned on the skin 28 tohave the focal volume 108 intersecting the biodegradablepouch/structure/patch 320 implanted near or into the tissue 333 that istargeted for the treatment inside the body 27, as shown in FIG. 33.

In embodiments, the biodegradable pouch/structure/patch 320 can beactivated via pressure shock waves at any time interval or intervals(multiple activations) after implantation via a percutaneous approach.Based on the depth where the biodegradable pouch/structure/patch 320 isimplanted the pressure shock waves reflectors 22 will have differentgeometries, with shallow reflectors 22 for less subcutaneous depthpenetration or deeper reflectors 22 for deep subcutaneous depthpenetration.

In order to cover the whole area of a drug delivery biodegradablepouch/structure/patch 320 the applicator 30 may have a longitudinalmovement 31 at the surface of the skin 28 following a predeterminedpattern that can be monitored by a designated computer program.

The controlled locally activated release of the drugs via pressure shockwaves can be very beneficial for the patient to avoid overdoses and toassure high efficiency of the treatment. In the same time, due to thehigh pressures generated during pressure shock waves the drugs can bepushed in the order of several millimeters away from the deliverysystem, which gives even more efficiency of the treatment. Also, at theend of the treatment a sufficient number of pressure shocks waves can bedelivered to provide a breakage of the biodegradablepouch/structure/patch 320 in small pieces that can be easily absorbed bythe tissue 333 and thus allowing a quicker re-implantation of a new drugdelivery biodegradable pouch/structure/patch 320 into the area, ifneeded.

Extracorporeal pressure shock waves may also be used for destruction oftissue hyperplasia, cysts and malignant tumors. Hyperplasia is definedas an abnormal increase in number of cells, which may result in thegross enlargement of an organ, such as the prostate when benign prostatehyperplasia or BPH occurs. The abnormal increase in number of cells canhappen to many types of tissues of the human/animal body 27 and cancreate pain, obstructions and abnormal functioning of certain organs ortissues.

A cyst is a closed sac, having a distinct membrane and division on thenearby tissue. It may contain air, fluids, or semi-solid material. Acollection of pus is called an abscess, not a cyst. Once formed, a cystcould go away on its own or may have to be removed through surgery.

Malignant neoplasms (cancer tumors) represent an abnormal mass of tissueas a result of neoplasia. Neoplasia is the abnormal proliferation ofcells. The growth of the cells exceeds and is uncoordinated with that ofthe normal tissues around it. The growth persists in the same excessivemanner even after cessation of the stimuli. It usually causes a lump orcancer tumor. Malignant neoplasm can be treated via medication,chemo-therapy, radiation, surgery or ablation.

Typical technologies used to ablate cysts and benign or malignant tumorsinclude using radio-frequency, high intensity focused ultrasound orcryogenic approaches. The main drawback for these technologies is theextreme heat or freezing temperatures generated during treatment thatcan affect adjacent tissues/organs and blood flow 39 circulation withunwanted side effects. After a procedure, the absorption of ablatedtissue by the body 27 is hindered by excessive inflammation, impairedblood circulation/flow 39, fluid accumulation, etc. Also, none of thesetechnologies are known to trigger a body reaction to heal the treatedarea.

Cavitation bubbles produced by pressure shock waves are collapsing withmicrojets powerful enough to penetrate the cancerous cellular membraneand thus destroying their integrity. This represents a “normal bodytemperature ablation” process that not employs high or low temperaturesused by the existing ablation technologies. Even more than that, theleakage of the cytoplasm content outside the cells triggers a localizedapoptosis mechanism and a immune response, which makes the body 27 torecognize the cancer cells that were invisible before and thus enhancingtumor destruction. Cavitation bubbles can be formed and/or induced bypressure shock waves only in fluids as water, blood, urine, etc. Inorder to promote/enhance the cavitation inside the body 27, salinesolution, contrast solution or drug cocktails can be injected in thetargeted treatment area as cysts, benign or malignant tumors. By usingthe drug cocktails with extracorporeal pressure shock waves, themicrojets generated by the collapse of the cavitation bubbles caneffectively push the drugs in the adjacent areas at high concentrationand thus enhancing their effects on the tumor in general. Furthermore,by applying a high number of shots (more than 2,000 shots per treatment)at high energy to the vasculature that feeds the tumor, the small bloodvessels and capillaries can be destroyed, which can be another way toshrink the tumors after the treatment with pressure shock waves.

Pressure shock waves can be also used for treating cancer in conjunctionwith microparticles or/and nanoparticles, which can be activated orpushed into the tissue via pressure shock waves in order to selectivelykill cancer cells or to deliver specific drugs and/or proteins and/orsubstances that can destroy the cancer cells.

Finally, the high energy pressure shock waves can be used to enhance thesensibility of the tumor cells to certain drugs and thus enhancing theircytotoxicity.

Based on the above observations, using a sufficient number of pressureshock waves (higher than 2000 shots) at high energies (flux densitieshigher than 0.3 mJ/mm²) and multiple treatments (at least two) appliedto a cyst, benign or malignant tumor a “normal body temperatureablation” can be realized using extracorporeal pressure shock waves.Applicators 30 such as those presented in FIGS. 5A, 5B, 6, 7, 10, 12A,12B, 14A, 14B and 33 may be used for the “normal body temperatureablation” using extracorporeal pressure shock waves. The ablation can beeither superficial or deep inside the human body 27 and must beprecisely coordinated and monitorized via ultrasound probes 37 orfluoroscopy.

Extracorporeal pressure shock waves may be used for fibrotic tissue,hyperthrophic lesions, organ adhesions, capsular contracture and tissuerepair/regeneration. Pressure shock waves used at the proper dosage andtreatment setting (medium to high energies, flux densities higher than0.1 mJ/mm²) are known to break down fibrous tissue or excessive tissueformed post-surgical as reparative or reactive processes of the body 27.This phenomenon can be used to repair: fibrotic tissue (excess fibrousconnective tissue in an organ or tissue generated by a reparative orreactive process), hyperthrophic lesions (increase in the volume of anorgan or tissue due to the enlargement of its component cells, which isdifferent from hyperplasia where the cells remain approximately the samesize but increase in number), organ adhesions (fibrous bands that formbetween tissues and organs, often as a result of injury during surgery,which may be thought of as internal scar tissue) and capsularcontracture (an abnormal response of the immune system to foreignmaterials, which forms capsules of tightly-woven collagen fibers arounda foreign body (breast implants, pacemakers 268, orthopedic jointprosthetics), tending to wall it off followed by the capsuletightening/contracture around the implant.

Pressure shock waves may also trigger body reaction (at low to mediumenergy settings, flux densities of less than 0.3 mJ/mm²) for healing viagrowth factors, stem cells activation and enhanced collateral bloodcirculation through new small arterioles and/or capillaries formation(angiogenesis). Such triggering may be used to produce the following:regeneration of burn tissue, repair of acute and chronic wounds, repairand regeneration of necrotic tissue due to ischemia (bone, soft tissue,skin, etc.), repair of bone fractures (acute or non-unions), repair ofpartial or total tears of cartilage, muscle, ligaments, tendons, etc.,regenerate the lining of the bladder for interstitial cystitis andreduce the symptoms, effects and treat auto-immune diseases as SystemicLupus Erythematosus, Ankylosing Spondylitis, Crohns Disease,Scleroderma, Dermatomyositis, etc.

Based on the foregoing descriptions, using a sufficient number ofpressure shock waves (higher than 500 shots), appropriate energy fluxdensities (as mentioned before) and multiple treatments (at least two),the suitable results can be realized using extracorporeal pressure shockwaves. Applicator embodiments (30, 200, 210, 220, 230) such as thosepresented in FIGS. 5A, 5B, 6, 7, 8A, 8B, 10, 12A, 12B, 14A, 14B, 20,21A, 21B, 22, 23A, 23B and 33 may be used for the treatment of fibrotictissue, hypertrophic lesions, organ adhesions, capsular contracture andtissue repair/regeneration. The pressure shock waves treatment can beeither superficial or deep inside the human body 27 (tuned to each typeof tissue treatment mentioned above) and must be precisely coordinatedand monitorized via ultrasound probes 37 or fluoroscopy.

Extracorporeal pressure shock waves may also be used for aseptic,bacterial, abacterial and viral infections or of parasites and harmfulmicro-organisms. When pressure shock waves were used for treatinginfected wounds it was noticed that they have a bactericidal effect,which helped with the healing and tissue repair. The effect of thepressure shock waves on Gram positive and Gram negative bacteria isenhanced due to the capacity of pressure shock waves to break thebiofilms formed by these bacteria. This is a major aspect of thetreatment using pressure shock waves due to the fact that they can allowthe treatment of most resistant infections, which are produced due tothe clustering of bacteria in biofilms and thus making bacterialinfections very difficult to treat with antibiotics or any other medicalmeans.

Also, studies have showed that the bacterial and viral capsule walls aremore susceptible to be disrupted and/or punctured by the pressure shockwaves (especially by the microjets produced during collapse of thecavitational bubbles) when compare to normal cells that make the bodytissues.

Furthermore, aseptic (sterile) loosening formed around implants orabacterial inflammation (as in abacterial prostatitis also known aspainful pelvic syndrome) can be treated using pressure shock waves forpushing inflammatory cells or inflammatory by-products out of thetreatment area and thus eliminate the active ingredients that produceinflammation and body reaction.

Fungal infections can be also treated using pressure shock waves inconjunction with appropriate medication, due to the capacity of pressureshock waves to disrupt the fungal films in places where the access isnot so easy—for example at the base of the toe nails.

Finally, parasites or harmful micro-organisms that can develop insidethe human/animal body 27 can be eliminated with appropriate pressureshock waves by damaging them or through disruption of their environment.

Depending on where the infection was developed, using a sufficientnumber of pressure shock waves (higher than 1,000 shots), appropriateenergy flux densities (higher than 0.2 mJ/mm²) and multiple treatments(at least two), the appropriate results can be realized usingextracorporeal pressure shock waves. Applicators (30, 200, 210, 220,230) such as those presented in FIGS. 5A, 5B, 6, 7, 8A, 8B, 10, 12A,12B, 14A, 14B, 20, 21A, 21B, 22, 23A, 23B and 33 can successfully beused for the treatment of aseptic, bacterial, abacterial and viralinfections or of parasites and harmful micro-organisms. The pressureshock waves treatment can be either superficial or deep inside the humanbody 27.

Extracorporeal pressure shock waves may be utilized for stem cells,genes treatment and nerve cells. When pressure shock waves were used fortreating infected wounds it was demonstrated that the dormant stem cellsare activated to participate in the repair mechanism. Also, scientificstudies showed that a stimulation of the stem cells in the harvestingareas from inside the human body 27 (periosteum, bone marrow, etc.) isproduced by the pressure shock waves. This allows the harvesting of anincreased population of stem cells that can be used for proliferationphase, thus making the process more efficient.

During proliferation phase a moderate mechanical stimuli produced by thepressure shock waves can be used to sustain an increased proliferationand thus a larger population of stem cells can be produced in a shorterperiod of time.

Based on the type of stem cells (human embryonic stem cells, adult stemcells or induced pluripotent stem cells) the energy generated by thepressure shock waves can be particularly tuned to produce thedifferentiation of the stem cells into desired cells necessary forimplantation into a specific type of tissue (bone, muscle, cartilage,etc.).

Furthermore, before stem cells implantation, during implantation orafter implantation the stem cells can be sustained in vivo by thepressure shock waves through enhanced blood flow 39 in the implantationarea through angiogenesis and by calling growth and repair factors.

The microjets generated by the collapse of the cavitation bubbles cancreate transient micro pores on living cells membranes and due toexisting pressure gradients produced by the pressure shock waves canestablish the optimum situation to push DNA fragments or genes insidethe cells. Specific genes can alter the behavior of the cells, whichmight turn out to be benefic. For example, the pancreatic beta isletcells (produce insulin and amylin) that are dysfunctional for type Idiabetic patients, through pressure shock wave gene treatment therestoring of physiological beta cell function could be accomplished.

Nerve cells assist with the correct functioning of the body 27 becausethey process and transmit information by electrical and chemicalsignaling from any region of the body 27 to the brain, for a harmoniousperception and functionality.

The pain generated by tissue disruptions or inflammation is perceived bythe peripheral nerve terminals and pressure shock waves are known toproduce an analgesic effect after few hundreds of shots, especially whenthe energy settings are gradually increased (ramping up process). Thisanalgesic effect can last for hours and may constitute an advantage whentreating chronic painful conditions. Furthermore, using special designedmicro-tubes to guide severed nerves, when multiple treatment usingpressure shock waves are applied, it was observed in animal studies thatthe nerves can grow from both ends and finally reunite to restore theirinitial function.

Depending on where the targeted cells (stem cells, nerve cells, etc.)are found inside the human/animal body 27, using a sufficient number ofpressure shock waves (higher than 750 shots), appropriate energy fluxdensities (higher than 0.1 mJ/mm²) and multiple treatments (at leasttwo), the desired results can be realized using extracorporeal pressureshock waves. Applicators (30, 200, 210, 220, 230) such as those shown inFIGS. 5A, 5B, 6, 7, 8A, 8B, 10, 12A, 12B, 14A, 14B, 20, 21A, 21B, 22,23A, 23B and 33 may be used for the stimulation, proliferation,differentiation of stem cells and their sustainability afterimplantation, for genes treatment or nerve cells stimulation (analgesiceffect) or for nerves regeneration and/or repair. The pressure shockwaves treatment can be either superficial or deep inside the human body27.

Extracorporeal pressure shock waves may be used in embodiments fordestruction of unwanted hard tissue. With advance in age and due traumaand different chronic diseases accumulation and/or deposits of hardtissue are created in specific area of the human body 27. Some examplesinclude: Bone spurs—are formed due to the increase in a damaged joint'ssurface area. This is most commonly seen from the onset of arthritis.Bone spurs usually limit joint movement and typically cause pain;heterotopic ossifications—is the process by which bone tissue formsoutside of the skeleton. Studies on heterotopic ossification havesuggested that it may be linked to injuries to the spinal cord, alongwith neurological conditions. The condition often appears in the form ofperiarticular ossification, especially around the site of hip injuries;and calcifications—is the process in which calcium salts build-up insoft tissue, causing it to harden. Calcifications may be classified onwhether there is mineral balance or not, and the location of thecalcification.

Debilitating accumulation of hard tissue in unwanted parts of the body27 can be treated using high energy pressure shock waves (energy fluxdensities higher than 0.3 mJ/mm²) with high number of shots (more than2,500 shots) and multiple treatment (more than three). The pressureshock waves treatment can be either superficial or deep inside the humanbody 27 (tuned to each type of tissue treatment mentioned above) andmust be precisely coordinated and monitored via ultrasound probes 37 orfluoroscopy.

Applicators (30, 200, 210, 220, 230) such as those presented in FIGS.5A, 5B, 6, 7, 8A, 8B, 10, 12A, 12B, 14A, 14B, 20, 21A, 21B, 22, 23A, 23Band 33 may be used for this type of treatment.

In embodiments utilizing shock waves in an intracorporeal approach,shock wave reflector 22 is preferably positioned on a catheter that mayhave radio-opaque markers 152, transducers, and the like, which helpwith positioning in the treatment area. The shaft of the catheter may bemulti-lumen to allow guide wire 94 access, fluid access in the reflector22 area, electrical connections, extraction of fluids/body fluids, etc.The intracorporeal approach requires the usage of a blood vessel 15 ornatural lumen of the human/animal body 27 or of an artificial createdopening/conduit, as is happening in laparoscopic procedures.

Embodiments of intracorporeal applications with pressure shock wavesinclude: treatment of total occlusions for major vessels (limited by thedimension of the catheter that carries the shock wave device inside theblood vessels) as independent intracorporeal pressure shock wavestreatment or in conjunction with drugs and/or extracorporeal pressureshock waves treatment; dissolution of blood clots (thrombus or embolus)from blood vessels (arteries and veins) and natural human/animalconduits/lumens as independent intracorporeal pressure shock wavestreatment or in conjunction with dissolution agents/drugs and/orextracorporeal pressure shock waves treatment; removal of blood vesselsstenotic plaques as independent intracorporeal pressure shock wavestreatment or in conjunction with drugs and/or extracorporeal pressureshock waves treatment; treatment to stabilize vulnerable plaques asindependent intracorporeal pressure shock waves treatment or inconjunction with drugs and/or extracorporeal pressure shock wavestreatment; treatment to reduce inflammation post angioplasty andstenting as an independent intracorporeal pressure shock waves treatmentor in conjunctions with drugs and/or extracorporeal pressure shock wavestreatment; treatment of blood vessels in-stent restenosis (blockage ofthe blood vessel after stenting due to regrowth of the smooth musclestimulated by post stenting inflammation), or in-stent restenosis forany natural human/animal conduit/lumen as an independent intracorporealpressure shock waves treatment or in conjunctions with drugs and/orextracorporeal pressure shock waves treatment; treatment to enhance drugdelivery to blood vessels and natural human/animal body internalconduits/lumens walls; treatment of the heart muscle via intracorporealapproach or transcutaneously as an independent intracorporeal pressureshock waves treatment or in conjunctions with drugs and/orextracorporeal pressure shock waves treatment and/or gene therapy and/orstem cells therapy; treatment to improve the functionality of themuscles that activate heart valves via intracorporeal approach ortranscutaneously as an independent intracorporeal pressure shock wavestreatment or in conjunctions with drugs and/or extracorporeal pressureshock waves treatment; treatment of aneurysms as an independentintracorporeal pressure shock waves treatment or in conjunctions withdrugs; treatment for occluded grafts (artificial or natural/harvested)as an independent pressure shock waves treatment or in conjunctions withdrugs and/or extracorporeal pressure shock waves treatment; treatment toreduce inflammation and repair internal lining of human and animalbodies natural conduits and cavities (as an independent intracorporealpressure shock waves treatment or in conjunctions with drugs and/orextracorporeal pressure shock waves treatment) including repair thelining of the bladder for interstitial cystitis, repair of the alllayers of the small intestine in Crohn's Disease, and repair of thesuperficial lining of the large intestine for ulcerative colitis;treatment to reduce tissue hyperplasia as for benign prostatehyperplasia (BPH) as an independent intracorporeal pressure shock wavestreatment or in conjunctions with drugs and/or extracorporeal pressureshock waves treatment; treatment to remove occlusions/obstructions fromhuman and animal bodies natural conduits and cavities (intracorporealpressure shock waves treatment alone or in conjunction with othersubstances/drugs and/or extracorporeal pressure shock waves treatmentand/or other therapies); liposuction system, which can avoid the sideeffects of the “golden treatment” HIFU liposuction as an independentintracorporeal pressure shock waves treatment or in conjunctions withextracorporeal pressure shock waves devices; treatment of benign ormalignant tumors using cavitation jets that can penetrate/break cellularmembranes and thus destroying benign or malignant cells using non-heatproducing mechanisms, as an independent pressure shock waves treatmentor in conjunctions with drugs and/or extracorporeal pressure shock wavestreatment; treatment to produce cellular apoptosis as an independentpressure shock waves treatment or in conjunctions with drugs and/orextracorporeal pressure shock waves treatment; and treatment to killinternal infections produced by Gram positive and Gram negativebacteria, viruses, fungus, etc., or parasites and micro-organisms fromall human body tracts that allows of introduction of a intracorporealpressure shock wave devices, as an independent intracorporeal pressureshock waves treatment or in conjunctions with drugs and/orextracorporeal pressure shock waves treatment including the following:urinary tract infections including (renal infections, bladder infection,bacterial or abacterial prostatitis), gastro-intestinal tract infectionsand respiratory tract infections.

In embodiments, the following characteristics may contribute to efficacyof treatment performed using intracorporeal pressure shock waves:

-   -   (1) Lateral exposure of the reflector to access        cavities/conduits wall.    -   (2) Frontal exposure of the reflector to access treatment area        frontally.    -   (3) Reflector aperture can be circular or elongated.    -   (4) The shape of the reflector may be shallow due to dimensional        constraints and can be in the form of an ellipsoid, sphere,        paraboloid, or planar. Any combination of two or more shapes can        also be used.    -   (5) Reflector dimensions (diametric) may be in the order of        2.5-10 mm, preferably 2.5-5 mm (miniature reflector) to        accommodate the vasculature/internal conduits dimensions.    -   (6) Position of the reflector may be in proximity of the distal        end of a catheter.    -   (7) The intracorporeal pressure shock wave catheter 340 may be        rotated around its central axis of symmetry. This rotation can        be achieved by having over-the-wire (guide wire 94) construction        or a rapid exchange solution, as shown in FIG. 34.

An over-the-wire solution has the guide wire 94 going through the wholelength of the intracorporeal pressure shock wave catheter 340 (from theproximal end 342 to the distal end 344 of the catheter), which helpswith a good guidance of the intracorporeal pressure shock wave catheter340 inside the vasculature or human body cavities, blood vessels 15 andnatural conduits/lumens. A drawback is that the long length (up to 190cm) can make the exchange of intracorporeal pressure shock wave catheter340 (retrieval from the guide wire 94 and replace with anotherintracorporeal pressure shock wave catheter 340) cumbersome. Also theguide wire 94 length must be twice the length of the intracorporealpressure shock wave catheter 340.

For rapid-exchange solution the guide wire 94 goes inside theintracorporeal pressure shock wave catheter 340 only for 5-30 cm of thedistal end 344 of the intracorporeal pressure shock wave catheter 340and for the rest of the length runs along the intracorporeal pressureshock wave catheter 340 inside the vasculature. This reduces the lengthof the guide wire 94 (now the length should be a little bid longer thanthe catheter not double the length) and the exchange of intracorporealpressure shock wave catheter 340 is done much faster. Theseconstructions complicate the distal end 344 design for theintracorporeal pressure shock wave catheter 340 and may impede centeringof the intracorporeal pressure shock wave catheter 340 inside the bloodvessels 15 or body conduits/lumens.

-   -   (8) The settings may be in the low energy scale (flux densities        of less than 0.1 mJ/mm²), due to the dimensions of the reflector        and also presence of the intracorporeal pressure shock wave        catheter 340 inside the human body 27. The range of actuating        voltages may be between few milivolts to hundreds of volts and        better in the order of volts. Also, more than 1,000 shocks are        preferable to achieve the appropriate results.    -   (9) Methods to produce pressure shock waves include        electrohydraulic, electromagnetic, piezoelectric, laser        discharge, explosive, mechanical, etc.    -   (10) Pressure shock waves can be focused, unfocused, radial,        planar, pseudo-planar, etc.    -   (11) The intracorporeal pressure shock wave catheter 340 will        access the vasculature through major arteries vs. femoral artery        (femoral access in the groin area) or brachial access (in the        appendage area). If needed, other non-traditional access points        might be used.

Intracorporeal pressure shock waves may be used for the treatment ofvulnerable and stenotic plaques, post angioplasty and post stentinginflammation, in-stent restenosis, heart muscle, drug delivery tohuman/animal body internal conduits/lumens and blood vessels walls,inflammation of human/animal body internal conduits/lumens and bloodvessels, and internal infections. The intracorporeal pressure shock wavecatheter 340 can be deployed inside the vasculature and usedindependently or in conjunction with drug boluses (mixture ofmedications) to treat vulnerable plaques 135 and stenotic plaques 130,in-stent restenosis 190, inflammation after angioplasty/stenting, bloodclots dissolution or to treat the tissue adjacent to the blood vessels15 (for example heart muscle, muscle that activate heart valves, etc.),as an independent intracorporeal pressure shock waves treatment or inconjunctions with drugs and/or extracorporeal pressure shock wavestreatment and/or gene therapy and/or stem cells therapy.

When intracorporeal pressure shock wave catheters 340 are placed insidea natural human/animal conduit/lumen, they can be used independently orin conjunction with drug boluses (mixture of medications) and/orextracorporeal pressure shock waves devices for reducing/eliminatingchronic inflammation, eradication of infections, or to promote healingand repair. Chronic inflammations can degenerate in cellular destructionand they are interconnected with infections and thus can havedetrimental effects on the human/animal bodies 27 and they need to beeliminated. It is well known that the pressure shock waves can reduceinflammation and also have a bactericidal effect (destroy bacteria),antiviral effect (destroy viruses) or antipathogen effect, which makethe intracorporeal pressure shock waves treatment a prime candidate totreat infections and chronic inflammations, as independent treatment orin conjunction with drugs and/or extracorporeal pressure shock wavesdevices and/or other therapies.

In the case of healing and repair an interstitial cystitis (painfulbladder syndrome), intracorporeal pressure shock waves catheters may beused to repair the defects in the lining (epithelium) of the bladder andthus reducing or eliminate the symptoms of this disease. Also, thepressure shock waves can have an analgesic effect on the nerves thattransmit the sensation of pain around the bladder, which can also helpwith the symptoms of this disease.

Artificial conduits may be used with intracorporeal pressure shock wavescatheters to treat percutaneously inflammation and infections or toreduce subcutaneous body fat layer, as in the case of liposuction.

When pressure shock waves are used to activate drug boluses an increasedconcentration of the drugs can be delivered in the treatment area forincreased efficiency, and thus avoiding systemic reaction given by thesame drug concentration when the boluses are delivered intravenously ororally. Activation of drug boluses with pressure shock waves can be doneeither intracorporeal or extracorporeal.

For electromagnetic discharge used to produce pressure shock waves, anactivator is needed which can increase the size of the intracorporealpressure shock wave catheter 340. If the intracorporeal pressure shockwave catheter 340 uses piezoelectric generated pressure shock waves, thebulkiness is reduced and thus the intracorporeal pressure shock wavecatheter 340 are smaller, which allows them to penetrate deeper intovasculature/blood vessels 15 (away from the heart 209) or in smallernatural/artificial human/animal conduits 17, which can give theadvantage of being able to treat areas that are not available for othertechnologies.

The electrohydraulic activation of the pressure shock waves may be usedfor any of the intracorporeal applications mentioned above due to theirsmallest diametric dimension when compared with the electromagnetic orpiezoelectric principle used to generate pressure shock waves using anintracorporeal pressure shock wave catheter 340.

FIG. 35 shows an intracorporeal pressure shock wave catheter 340functioning on the electrohydraulic principle. The intracorporealpressure shock wave catheter 340 has at the proximal end 342, accessports 354 to allow the introduction of the guide wire 94 (for“over-the-wire” construction) and for introduction/extraction of fluidfrom the intracorporeal catheter shock wave applicator area 350. Thestrain relief 352 is used to allow the transition from the access ports354 to the body of the intracorporeal pressure shock wave catheter 340without kinking. The distal end 344 of the intracorporeal pressure shockwave catheter 340 has the intracorporeal catheter shock wave applicator350, where the pressure shock waves are produced. Also, forvisualization and correct positioning in the treatment area, the distalend 344 of the intracorporeal pressure shock wave catheter 340 hasradio-opaque markers 152 and a radio-opaque tip 90.

For electrohydraulic principle (FIG. 35), the electrical discharge canbe produced directly in blood from blood vessels 15 or in any fluidpresent in natural human/animal conduits/lumens or in enclosed waterfilled (saline solution filled) chambers or spaces in the intracorporealcatheter shock wave applicator 350. To have consistency of thedischarge, the discharge in water or saline solution is preferred. Inembodiments, the intracorporeal catheter shock wave applicator 350 ispre-filled or can be filled with saline solution at “the point of care”using the two saline lumens (saline “IN” lumen 365 and saline “OUT”lumen 366), as shown in FIG. 36B. Filling at “the point of care” ispreferred to reduce the size of the intracorporeal pressure shock wavecatheter 340 during advancement through vasculatures (blood vessels 15)or natural/artificial human/animal conduits/lumens, as shown in FIGS.36A and 36B.

In embodiments of the invention, direct contact of the intracorporealcatheter shock wave applicator 350 is made with the plaques 130(stenotic plaques or vulnerable plaques) or targeted area of naturalhuman/animal conduit/lumen for pressure shock waves treatment. Forvasculature treatment this approach can be used for the vessels 15 inthe body appendage 25, where the generation of small particles from theplaques 130 (stenotic plaques or vulnerable plaques) can flow down theblood stream without any life threatening consequences. In embodimentsto completely treat the plaques 130 (stenotic plaques or vulnerableplaques from blood vessels) or targeted area of natural human/animalconduit/lumen, the intracorporeal pressure shock wave catheter 340 mayallow axial movement and rotational movement around the guide wire 94(the catheter needs to be stir-able) and facilitate the focal volume 108intersecting the plaques 130 (stenotic plaques or vulnerable plaquesfrom blood vessels 15) or targeted area of natural human/animalconduit/lumen. Shock waves are generated in electrohydraulic embodimentsby discharging voltage on the spark gap 362.

In order to protect the distal vasculature from any pieces of plaque 130(stenotic plaque or vulnerable plaque) that might be dislodged from theblood vessel 15 wall, the treatment with intracorporeal pressure shockwaves may be combined with distal protection devices, such as presentedin FIG. 37.

The distal protection system shown in FIG. 37 includes an occlusionballoon 154 utilized to collect debris 95 generated duringintracorporeal pressure shock wave treatment. The extraction ofcollected debris 95 is done using passive suction (manual syringeactivated—not pumps) to prevent the blood flow 39 or normal flow fornatural conduits/lumens to carry the debris 95 down the stream, whichmight create blockages. The steps to perform such a procedure in oneembodiment include:

-   -   (A) Guide wire 94 introduction through femoral and brachial        access.    -   (B) Set guide wire 94 in the plaque 130 (stenotic plaque or        vulnerable plaque from blood vessels 15) or targeted area of        natural human/animal conduit/lumen 17.    -   (C) Introduce the guide catheter 92 over the guide wire 94 and        set the distal end of the guide catheter 92 proximal to the        treatment area using the radio-opaque tip 90 of the guide        catheter 92.    -   (D) Using the guide wire 94 slide the intracorporeal pressure        shock wave catheter 340 inside the guide catheter 92 towards the        treatment area.    -   (E) Set the intracorporeal pressure shock wave catheter 340 in        front of the plaque 130 (stenotic plaque or vulnerable plaque        from blood vessels 15) or targeted area of natural human/animal        conduit/lumen using the catheter radio-opaque markers 152 (not        shown in FIG. 37) and the radio-opaque tip 90. This procedure        allows the focal volume 108 to properly intersect the treatment        area.    -   (F) Fill in the intracorporeal catheter shock wave applicator        350. Push saline solution and contrast media mixture through the        “IN” lumen 365 and saline until it comes back to the “OUT” lumen        366. Block the “OUT” lumen 366 and fill in the intracorporeal        catheter shock wave applicator 350 at the required pressure        (1-10 psi) using the “IN” lumen 365. The membrane 205 should now        be in contact with plaque 130 (stenotic plaque or vulnerable        plaque from blood vessels 15) or targeted area of natural        human/animal conduit/lumen.    -   (G) Inflate the guide wire 94 occlusion balloon 154 with saline        solution and contrast media mixture.    -   (H) Perform the shock wave treatment by discharging voltage on        the spark gap 362 in order to create, focused shock waves 372.        Move intracorporeal pressure shock wave catheter 340 up and down        and rotate it to cover the whole treatment area.    -   (I) After finishing the treatment retrieve the intracorporeal        pressure shock wave catheter 340 and use the guide catheter 92        to perform passive suction through the suction area 374 in order        to collect any possible debris 95.    -   (J) After extraction of 2-3 syringes of 60 ml of blood/fluid        from the treatment area through the suction area 374, deflate        the guide wire 94 occlusion balloon 154.    -   (K) Retrieve the guide catheter 92 and the guide wire 94.    -   (L) Close the access (femoral or brachial).

In embodiments, the suction is done after the treatment with pressureshock waves was finished and after the intracorporeal pressure shockwave catheter 340 is removed from the treatment area, allowing a largerlumen to be used for suction (larger suction area 374 shown in FIG. 37).

Another option for distal protection includes use of designed debriscollection basket 35 to collect debris 95, as shown in FIG. 38. Thedebris collection basket 35 opens and closes based on an umbrellamechanism and it is attached to a guide wire 94. In this case the guidecatheter 92 is used to guide the intracorporeal pressure shock wavecatheter 340 through vasculature and not for suction as in the distalprotection solution that uses the occlusion balloon 154 of the vessel15, as presented in FIG. 37. The big advantage of the debris collectionbaskets 35 is that they allow blood flow 39 through them duringtreatment and in the same time the debris 95 collection, in contrast toocclusion balloon 154 solution where no blood flow 39 is allowed untilthe treatment is finished, and debris 95 collected via suction.

The treatment set-up, generation of the pressure shock waves,positioning under fluoroscopic guidance of the guide catheter 92 andintracorporeal pressure shock wave catheter 340 in the treatment areaand post treatment steps are similar to those presented in explanationsfor the FIG. 37.

Another approach (the third) is provided by the distal protectiondevices that use multiple occlusion balloons (first occlusion balloon154 and the second occlusion balloon 156) as presented in FIG. 39, wherethe catheter shock wave applicator 350 has a membrane 205 andpropagation of pressure shock waves is done through blood. Collection ofdebris 95 is done through active flushing with saline using IN opening392 and OUT opening 394 positioned in between the two occlusion balloons(154 and 156). The active flushing is done by extracorporeal dedicatedpumps. The correct positioning of the intracorporeal pressure shock wavecatheter 340 in the treatment area of the blood vessel 15 or naturalconduit/lumen is done using the radio-opaque markers 152 and the twoocclusion balloons (154 and 156) that are filled with saline andcontrast media solutions.

In another embodiment presented in FIG. 40, different from thosepresented in FIGS. 36A, 36B, 37, 38 and 39, a space is created inbetween first occlusion balloon 154 and the second occlusion balloon 156and the blood is evacuated from the enclosed space and replaced withsaline solution to allow a better formation of cavitation bubbles by thefocused pressure shock waves 372. Compared to FIG. 39 where thedischarge is produced in a protected space under a membrane 205, theembodiment in FIG. 40 using an electrohydraulic generator permits thevoltage discharge to occur in the saline solution trapped between thetwo balloons 154 and 156 without the protection of a membrane 205. Inother words, reflector 402 of the intracorporeal pressure shock wavecatheter 340 is exposed to the saline solution trapped between the twoballoons 154 and 156.

At the end of the treatment, IN lumen 365 and OUT lumen 366 (FIG. 36B),may be used to bring and extract the saline solution into and from theclosed space and can be also used for flushing the area of possibledebris 95 via active flushing using dedicated pumps.

In another embodiment presented in FIG. 41, reflector 402 isincorporated inside an occlusion balloon 154, which can be filled withhigh pressure saline solution or saline solution plus contrast forvisualization inside the body 27. Thus the occlusion balloon 154 canhave a dual treatment purpose of: (1) balloon used to push the plaque130 (stenotic plaque or vulnerable plaque) or the targeted area radiallyand thus opening the cross-sectional area of the blood vessel 15 or theconduit/lumen; and (2) usage of the same balloon to treat with pressureshock waves.

In embodiments, the pressure shock waves can be delivered in fullyinflated balloons or partially deflated balloons. Additionally, theballoon can be designed in such a way that its diametric dimension atfull inflation is less than the blood vessel 15 or the conduit/lumendiameter. In the described embodiment, the catheter is dedicated forpressure shock waves only and can be used to treat plaques 130 (stenoticplaques or vulnerable plaques of a blood vessel 15) or in-stentrestenosis 190. The same embodiment presented in FIGS. 39, 40 and 41 canbe used to treat chronic inflammation, hyperplasia or in-stentrestenosis 190 for any natural human/animal conduits/lumens, asindependent intracorporeal pressure shock waves treatment or inconjunction with drugs and/or extracorporeal pressure shock wavesdevices and/or other therapies.

If the occlusion balloon 154 from FIG. 41 has a controlled porosity 415,medication can be pushed out from the occlusion balloon 154 due topressure shock waves. This approach can be used to push medication mucheasier than a passive mean into the plaques 130 (stenotic plaques orvulnerable plaques of a blood vessel 15) or in targeted area for anynatural human/animal conduits/lumens. The medication can help withreducing inflammation, blocking smooth muscle cells proliferation,relaxation of vessel 15 or natural human/animal conduit/lumen wall, etc.

The positioning of the intracorporeal pressure shock wave catheter 340inside the vasculature or natural human/animal conduits/lumens is doneusing radio-opaque markers 152 incorporated in the catheter body (aspart of plastic mixture or by adding metallic bands, dots, etc) and theradio-opaque tip 90 of the intracorporeal pressure shock wave catheter340.

For the treatment of vulnerable plaque and stenotic plaque, postangioplasty and post stenting inflammation, in-stent restenosis 190,heart muscle, drug delivery to human/animal body internalconduits/lumens and blood vessels 15 walls, inflammation of human/animalbody internal conduits/lumens and blood vessels 15, and internalinfections, the settings of the intracorporeal pressure shock wavescatheter 340 should be for the dosage of more than 500 shots, at energyflux densities higher than 0.001 mJ/mm² and frequencies of the pulsesbetween 1 Hz and 10 Hz.

Intracorporeal pressure shock waves may be further used to treataneurysms of the blood vessels. When the radial and tangential strengthis lost, the blood vessels 15 start to balloon, which creates aneurysmsThe reduced strength of the blood vessels 15 wall makes them prone toballoon that can ultimately results in the blood vessels 15burst/rupture under normal blood pressure, which can be fatal especiallyfor major blood vessels as aorta. When an aneurysm develops it istypically treated via surgery or endovascular approach with multiplecombinations of stents 170 covered with graft material. Based ondemonstration efficacy of the pressure shock waves to grow tissue, thereis a favorable possibility of reinforcing the wall of the aneurysm usingan intracorporeal pressure shock waves device.

Aneurysms can form in brain (genetic predispositions and anomalies). Dueto the sensitive area and the very small dimensions of the bloodvessels, the intracorporeal pressure shock waves catheters 340 are notpreferable for brain aneurysms. If pressure shock waves are needed totreat brain area, the device should preferably be extracorporeal.

Big blood vessels walls (especially aorta, iliacs, femoral arteries,etc.) can lose their radial strength due to genetic problems, nutrition,age, etc. If aneurysms in aorta grow too big, they can rupture, whichcan be fatal if not treated immediately. The aneurysms in the iliacs arenot fatal, but they create important health problems.

Aortas are big blood vessels 15 up to 35 mm and iliacs can get close to18 mm in diameter. This gives the advantage of using largerintracorporeal pressure shock waves catheters 340 with bigger reflectorsfor pressure shock waves that can be introduced into vasculature viafemoral access.

Most aneurysms 420 are found in aorta (thoracic aneurysms 421 andabdominal aneurysms 422) and in the iliacs (iliac aneurysms 423), asshown in FIG. 42. The intracorporeal pressure shock waves catheter 340can reach an outer diameter of about 7-8 mm for the treatment of aorticaneurysms (421 and 422) and iliac aneurysms 423.

Aneurysms' 420 treatment with any of the intracorporeal pressure shockwaves' catheters 340 presented previously in FIGS. 35, 36A, 36B, 37, 38,39, 40 and 41 may be used. Due to increased dimensions for theintracorporeal pressure shock waves catheter 340 and the necessaryincrease in efficiency, multiple reflectors (402 and 404) may also beused, as presented in FIG. 43.

Reflector 402 and reflector 404 are in communication to allow the salinesolution to move “in” and “out” for both reflectors 402 and 404simultaneously.

Multiple reflectors can increase efficiency as the treatment is givensimultaneously in multiple points of the aneurysm 420, where the focalvolumes 108 intersect the aneurysm 420 wall. Referring to FIGS. 43 and44, independent reflectors (402 and/or 404) are disposed 180° apart(opposite). Electrical wires 432 are provided within catheter 340. Ifthe environment permits, the reflectors can be at 120° angle separationand even better at 90° angle separation. FIG. 44 shows an embodimentwhere multiple reflectors (three reflectors 402 and three reflectors404) are disposed inside a dedicated non-occlusion balloon 440 thatallows the electrohydraulic discharge in saline solution 445 instead ofblood, which can increase the efficiency of the pressure shock wavestreatment. The length of the non-occlusion balloon 440 that incorporatesthe pressure shock waves reflectors (402 and 404) is dictated by thesize of the aneurysm 420 that must be treated and can vary from 5-15 cm.The saline solution 445 is brought IN and OUT via small tubes of plastic(saline “IN” tube 441 and saline “OUT” tubing 443), glued on the body ofthe intracorporeal pressure shock waves catheter 340. The material ofthe non-occlusion balloon 440 should be able to sustain high pressures(for example nylon or other materials used for angioplasty balloons).

In FIG. 44 the non-occlusion balloon 440 is illustrated in directcontact with the aneurysm 420, although the design could be done in suchway to not push against the wall of the aneurysm 420, as presented inFIG. 45. The only role for the non-occlusion balloon 440 is to providean enclosed chamber in which the pressure shock waves can be generatedin more efficient way. For both FIGS. 44 and 45 the material of thenon-occlusion balloon 440 should be a very good acoustic transmissionmaterial, to not impede in pressure shock waves propagation andfocusing. The controlled pressure inside the non-occlusion balloon 440may maintain a certain dimension of the balloon, its integrity and inthe same time optimal propagation of the pressure shock waves.

Referring to FIG. 45 the difference between the shaft of theintracorporeal pressure shock waves catheter 340 and the outer diameterof the non-occlusion balloon 440 may be minimal (difference of 2-5 mmradial). In this way, the non-occlusion balloon 440 will not contact theaneurysm 420 wall. In some embodiments, the intracorporeal pressureshock waves catheter 340 is centered inside the blood vessel 15 to allowthe treatment of the aneurysm 420 wall. In other words it is wanted thatthe focal volumes 108 to intersect the aneurysm 420 wall to provide agood treatment.

Note that the solution presented in FIG. 45 does not have a guide wirelumen 367 (FIG. 43). The guiding of the intracorporeal pressure shockwaves catheter 340 into the treatment area is made by the guide catheter92. Initially a guide wire 94 was used to allow the correct positioningand advancement of guide catheter 92 inside vasculature by gliding overthe guide wire 94. After this step, the guide wire 94 was retrieved andfinally the intracorporeal pressure shock waves catheter 340 is set inplace by sliding it inside the guide catheter 92.

As shown in FIG. 45, multiple points of origin (discharge points 68) forpressure shock waves can be used in a single cavity (such as pipe withellipse cross-section) used for reflection and focusing of the pressureshock waves. In this embodiment, the efficiency is improved in treatingthe aneurysm 420 with multiple focal volumes 108. To cover the wholeaneurysm 420 the intracorporeal pressure shock waves catheter 340 mustbe moved axially and rotate 360°, under fluoroscopic guidance usingcatheters' radio-opaque markers 152 (not shown in FIG. 45) and theradio-opaque tip 90. The intracorporeal pressure shock waves catheter340 is introduced and guided inside the blood vessel 15 via a guidecatheter 92. The non-occlusion balloon 440 is inflated and deflated withsaline solution via the “IN” lumen 365 and “OUT” lumen 366.

In a further embodiment, the body of the intracorporeal pressure shockwaves catheter 340 can be made in the form of a reflective geometryshown in FIG. 46. The catheter reflector 460 is made of a hypotube (thinmetal tube) shaped in the form of a pipe with ellipse or a parabolacross-section that can focus away pressure shock waves generated by thedischarge points 68 (F₁,F₂,F₃,F₄, and F₅).

A radio-opaque key/marker 152 (as shown in FIGS. 40 and 41) on theproximal end of the intracorporeal pressure shock waves catheter 340, inthe form of a line or a marker point, will allow the user to know theproper alignment of the intracorporeal pressure shock waves catheter 340against the vessel 15 wall needing treatment.

For embodiments shown in FIGS. 43, 44, 45, and 46, the multiple pointsof origin for the shock waves (multiple reflectors 402 and/or 404 ormultiple discharge points 68, in one reflector) can be controlled viasoftware, which allows the firing simultaneously of each point of originor sequentially in a predetermined pattern by the controller 462.

For the treatment of aneurysms 420 in blood vessels the settings of theintracorporeal pressure shock waves catheter 340 should be for thedosage more than 2000 shots, at energy flux densities higher than 0.01mJ/mm² and frequencies of the pulses higher than 2 Hz.

The following characteristics may contribute to successful treatment ofocclusions 20 and blood clots with intracorporeal pressure shock wavestreatment (as seen in FIGS. 47A, 47B and 47C):

-   -   1) Frontal exposure of the pressure shock waves reflectors (471,        472 or 473), positioned at the intracorporeal pressure shock        waves catheter 340 distal end.    -   2) Microjets produced by collapse of the cavitation bubbles        represent a main mechanism of action to treat occlusions 20 and        blood clots.    -   3) The focal volume 108 of the intracorporeal pressure shock        waves catheter 340 (where the cavitation is formed) must        intersect the occlusion 20 or the blood clot in order for the        intracorporeal pressure shock waves treatment to be efficient.    -   4) The dimensions of the reflectors (471, 472 or 473) and their        optimal orientation (perpendicular to the occlusion 20 or blood        clot) will dictate the efficiency of the intracorporeal pressure        shock waves.    -   5) The small area available to focus intracorporeal pressure        shock waves (dictated by the blood vessel 15, conduit/lumen or        artificial vessel 184 cross sectional area) can reduce the        amount of energy delivered in one shot by the intracorporeal        pressure shock waves catheter 340, when compared to        extracorporeal pressure shock waves devices (larger area at        their disposal to focus pressure shock waves). This is why the        intracorporeal pressure shock waves catheter 340 may need to use        an increased number of shots per treatment.    -   6) The voltage used for actuating the intracorporeal pressure        shock waves catheter 340 is in the range of milivolts to        hundreds of volts.    -   7) If the actuating voltage for the intracorporeal pressure        shock waves catheter 340 used for occlusions 20 and blood clots        is small enough, battery operating devices may be used in such        applications.    -   8) The reflectors (471, 472 or 473) may be created from        materials such as, but not limited to metal, hard plastics or        ceramics/glass.    -   9) Combination of pressure shock waves and drugs can be used to        enhance treatment efficiency by using the synergy of pressure        shock waves with the drugs.    -   10) Various methods to produce pressure shock waves include        electrohydraulic, electromagnetic, piezoelectric, laser        discharge, micro-explosion/discharge or mechanical vibrations.    -   11) The electrohydraulic discharge, laser discharge or        micro-explosion/discharge may be made in water, and avoid blood,        for increased efficiency    -   12) The shape of the reflector can be elliptical, paraboloid,        sphere or planar, or combinations of them.    -   13) The intracorporeal pressure shock waves catheter 340, due to        the position of the reflectors 471, 472 or 473 (frontal        exposure), do not allow guide wires 94 usage. The guidance of        the intracorporeal pressure shock waves catheter 340 may be done        through guide catheters 92. If a guide wires 94 is used that        will reduce the dimensions of the reflectors 471, 472 or 473 and        the reflective area necessary to focus pressure shock waves.    -   14) Consistent with described exemplary embodiments, the        construction of the intracorporeal pressure shock waves catheter        340 walls preferably allows electrical insulation of that        patient.    -   15) The access of the intracorporeal pressure shock waves        catheter 340 for blood vessels 15 or grafts/artificial vessels        184 to treat occlusions 20 and/or blood clots may occur through        femoral or brachial points.    -   16) For occlusions 20 and blood clots of the natural        human/animal conduits/lumens, access to the occlusion 20 or        blood clot may be via the conduit/lumen.    -   17) The size of the intracorporeal pressure shock waves catheter        340 might restrict the use of the intracorporeal pressure shock        waves technology for certain sizes of blood vessels 15 ort        conduits/lumens or grafts/artificial vessels 184.    -   18) If possible in embodiments, a pivotal movement of the        reflectors (471, 472 or 473) may allow the orientation of the        cavitation microjets on a larger area of the occlusion 20 or        blood clot and thus improved efficiency can be achieved.    -   19) If needed, the debris 95 generated during elimination of the        occlusion 20 or blood clots using the intracorporeal pressure        shock waves catheter 340 can be collected using passive or        active suction. Distal protection baskets 35 can be also used,        although they need a point of access distal to occlusion 20 or        blood clot, which is more difficult to achieve. For treating        vascular occlusions 20 or blood clots in body appendages 25 ,        the danger of debris 95 going down the blood flow 39 stream is        less important in comparison to carotid or coronary arteries.

When an ellipsoid is used for pressure shock waves reflecting area (FIG.47A) the intracorporeal pressure shock waves catheter 340 will have anellipsoidal reflector 471. For the ellipsoidal reflectors 471, the ratioof semi axis should be larger than 2.0 (c/b≥2). This ratio will allowthe focusing and formation of the cavitation in front and on occlusion20. A higher ratio of semi axes will also allow having a deeperellipsoidal reflectors 471 incorporated into the tip of theintracorporeal pressure shock waves catheter 340, which translates intoa larger reflecting area and higher efficiency for the intracorporealpressure shock waves.

When a sphere is used as a reflector, the intracorporeal pressure shockwaves catheter 340 may have a spherical reflector 472, as seen in FIG.42B. These types of reflectors create radial wave 474. Cavitation maystill be developed by the spherical reflector 472, although thepenetration of the compressive pressure waves is reduced, when comparedwith focused pressure shock waves. The energy of the radial pressurewaves is the highest in the center of the sphere and it dissipates veryfast during propagation away from the point of origin (center of thesphere). In this case, a close proximity or contact of theintracorporeal pressure shock waves catheter 340 with the occlusion 20or blood clot is needed.

Note that for each situation presented above, to eliminate debris 95generated during pressure shock waves treatment, a passive or activesuction can be realized through the guide catheter 92 (using the spacein between the interior surface of the guide catheter 92 and externalsurface of the intracorporeal pressure shock waves catheter 340, whichdefine a suction area 374). Passive suction is done using syringes(manual) for extraction of debris 95 trapped in front of the occlusion20 or blood clot. Active suction is generated using dedicated pumps thatcontinuously extract the mixture of debris 95 generated during treatmentwith blood or fluid present inside blood vessel 15, graft or artificialvessel 184 or human/animal body conduit/lumen, during intracorporealpressure shock waves treatment. To facilitate an easy discharge, thereflectors (471, 472 or 473) have a thin membrane 205 (not shown inFIGS. 47A, 47B or 47C) on top of them, which creates an enclosed spacefilled with a fluid. The fluid can be degassed water, saline solution orsaline/contrast mixture and can be filled at the manufacturer(pre-filled catheter) or can be done at “the point of care”. When thereflector (471, 472 or 473) is pre-filled at the manufacturer,additional substances might be added into the water/saline solution toimprove efficiency of the pressure shock waves generation or forimproved visualization of the catheter head inside the human body 27(any contrast agent). As can be seen from FIGS. 47A, 47B and 47C, thereare two distinctive channels (inlet lumen 365 and outlet lumen 366) thatcan be used to fill in the reflectors (471, 472 or 473) and to allow theclearing of air from the intracorporeal pressure shock waves catheter340. If air is not cleared from the reflectors (471, 472 or 473) theefficiency of the pressure shock waves can be greatly reduced.

FIG. 47C presents a solution of a movable pressure shock waves reflectoror bellowed reflector 473. The angular movement of the bellowedreflector 473 is realized by pulling at the proximal end of theintracorporeal pressure shock waves catheter 340 the two sutures 478 and479 that run through the catheter body length and are connected to thelateral ears of the reflector. If suture 478 is pulled, then thebellowed reflector 473 will rotate upwards. If suture 479 is pulled,then the bellowed reflector 473 will rotate downwards. The rotationtakes place around the “living hinge” 477 through which the bellowedreflector 473 is connected to the intracorporeal pressure shock wavescatheter 340 body. The bellows 476 act as a spring, which brings backthe bellowed reflector 473 in straight position when the sutures (478and 479) are released from the tensional (pull) position.

Radio-opaque markers 152 (not shown in FIGS. 47A, 47B and 47C) on theintracorporeal pressure shock waves catheter 340 can be used to positionthe catheter in the desired position relatively to the occlusion 20 orblood clot. In general, the pressure shock waves should be started awayfrom the occlusion 20 or blood clot and gradually close in.

To further increase efficiency of the intracorporeal pressure shockwaves treatment, the reflective area can be increased in embodiments ofthe invention by using a nitinol reflector that flowers inside the body27 at 37° C. (body temperature), although at the introduction in theblood vessel 15 or body conduit or lumen its dimension is relativelysmall. Nitinol (alloy of nickel and titanium) is a temperature memorymetal that was used in the last decades successfully in the constructionof self-expandable stents 170. Practically, using lasers differentpatterns are cut on nitinol small diametric tubes (hypo tubes), whichthen are expended gradually to the desired functional dimension. Thisfinal achieved shape and dimension is kept only at body temperature, dueto the memory of the nitinol.

If the tube is cooled down it will get back to the initial shape anddimension. This process is used to crimp the stents 170 on thetransporting catheters (process of capture the stents 170 at theirlowest diameter inside a sheath 481 and on a delivery/transportingcatheter shaft called catheter inner member 485), as can be seen fromFIG. 48. This figure shows a crimped nitinol stent 170 underneath thesheath 481 that is deploying inside a blood vessel 15 or a naturalhuman/animal conduit/lumen 17. After the intracorporeal pressure shockwaves catheter 340 is advanced in the treatment area, the sheath 481that covers the stent 170 is moved backwards using a push-pullmechanisms or screw-nut mechanisms. By pulling the sheath 481 from thetop of nitinol stent 170, the stent reacts to the body temperature andgets immediately from the crimped state to full temperaturepre-programmed dimension and shape (deployed shape 483). The zone oftransition from crimped state to the largest dimension is called“flowering region” 487.

Based on the same principle, a nitinol reflector can be created that canbe crimped on an inner member 485 of the intracorporeal pressure shockwaves catheter 340 and stays in that folded position until the desiredtreatment area is reached. At that point, the sheath 481 is pulled backand allows the extension of additional surface for the pressure shockwaves reflector, which can increase its efficiency. This reflectorcalled “tulip reflector” 490 (as seen in FIGS. 49A and 49B) canpenetrate small blood vessels 15 or grafts/artificial vessels 184 orsmall natural conduits/lumens 17 due to its reduced diametric dimensionin the crimped state. After the usage/treatment, the “tulip reflector”490 can be retracted in the sheath 481 to allow the safely removal ofthe intracorporeal pressure shock waves catheter 340 from blood vessels15 or grafts/artificial vessels 184 or small natural conduits/lumens.

The “tulip reflector” represents an advantageous embodiment forintracorporeal pressure shock waves treatment of occlusions 20 and bloodclots. The nitinol “tulip reflector” 490 design/approach can be mainlyused with the electrohydraulic principle for generating pressure shockwaves, although the piezoelectric principle can be also used, if theleaves of the reflector are covered with a thin piezoelectric layer(crystals or fibers).

For the electrohydraulic devices, a laser discharge is used to createthe pressure shock waves. The discharge is done in blood for vascularocclusions 20 and lysis of the blood clots, which is not as efficient asthe voltage discharge in water. This is why is much better to isolate aspace in front the occlusion 20, evacuate the blood and replace it withsaline solution. For that an occlusion balloon 154 must be present onthe guide catheter 92 to create an enclosed chamber in between theballoon and occlusion 20.

For the occlusions 20 and blood clots of the natural human/animalconduits/lumens, the saline solution may be injected in the targetedarea to facilitate the electrohydraulic discharge.

The “tulip reflector” 490 presented in FIGS. 49A and 49B is preferablymade of nitinol and in order to better preserve dimensional integrityduring pressure shock waves emission and focusing, may have a thinpolymeric membrane on the outside of the reflector that can easily foldduring crimping process without adding significant to diametricdimension of the delivery catheter. Similar thin polymeric membranes mayalso be used in the distal protection baskets 35 in embodiments. Apolymeric thin membrane (on the outside of the “tulip reflector” 490)seeks to ensure the “tulip reflector” 490 will not over extend itsleaves under the dynamic pressure generated by the shock waves, whichtranslates in preserving its precise focusing ability.

FIGS. 49C, 49D and 49E show the usage of the “tulip reflector” 490 totreat occlusions 20 and blood clots inside blood vessels 15 orgrafts/artificial vessels 184 or small natural conduits/lumens.

FIG. 49C shows how the positioning relative to the occlusion 20 or bloodclot is accomplished using the radio-opaque tips 90 of the sheath 481and of the guide catheter 92. The crimped “tulip reflector” 490 being ametallic alloy is preferably visible under fluoroscopy.

In FIG. 49D the deployed “tulip reflector” 490 is shown to generatefocused shock waves 372 during treatment of occlusion 20 or blood clot.Sheath 481 is pulled back in order to allow the flowering of the “tulipreflector” 490 that is attached to the inner member 485. The potentialdebris 95 generated during treatment can be extracted via active orpassive suction through the suction area 374 created in between theguide catheter 92 and the sheath 485.

The capture of the “tulip reflector” 490 inside the sheath 481 andretrieval from the blood vessel 15 or grafts/artificial vessels 184 orsmall natural conduits/lumens is shown in FIG. 49E. Suction is continuedthrough the suction area 374 even after the pressure shock wavestreatment was finished in order to avoid the flowing of the debris 95(not shown in FIG. 49E) down the stream.

Eight (8) steps are used in one embodiment of the invention foradvancing the tandem of guide catheter 92 and the “tulip reflector” 490inside the sheath 481 in order to create an enclosed chamber forpressure shock waves in the treatment area, for performing the treatmentof an occlusion 20 or blood clot using the “tulip reflector” 490, andfinally for retrieval of the guide catheter 92 and “tulip reflector” 490from the blood vessel 15 or graft/artificial vessel 184 or small naturalconduit/lumen are presented in detail in FIGS. 50A, 50B, 50C and 50D.

Step (1) is shown in FIG. 50A where: guide catheter 92 is inserted inthe blood vessel 15 or graft/artificial vessel 184 or small naturalconduit/lumen over a guide wire 94. When the desired position is reachedusing fluoroscopy guidance, the radio-opaque tip 90 of the guidecatheter 92 should be 3-7 cm before the occlusion 20 or blood clot. Inthis position the occlusion balloon 154 of the guide catheter 92 isinflated (with saline solution or saline and contrast mixture) and anenclosed chamber is created.

Step (2) is shown in FIG. 50B, in which the blood from the enclosedchamber crated in Step (1) is emptied via guide catheter 92 lumen andreplaced with saline solution introduced via “IN” tubes 441. Guide wire94 is retrieved in one embodiment before starting the process ofreplacing the blood with saline solution or mixture of saline andcontrast agents.

FIG. 50C shows Step (3) in which the intracorporeal pressure shock wavescatheter 340 (composed out of the sheath 481, inner member 485 with the“tulip reflector” 490 at its distal end) is introduced in the treatmentarea in close proximity of the occlusion 20 or blood clot. The correctpositioning should be distal from the guide catheter 92 and can bedetermined using the radio-opaque tips 90 of the sheath 481 and guidecatheter 92.

Step (4) is shown in FIG. 50D, in which the “tulip reflector” 490 wasdeployed by retrieving the sheath 481 and focused pressure shock waves372 are generated by the “tulip reflector” 490. In order for thetreatment to be efficient, the focal volume 108 should intersect theocclusion 20 or blood clot. The debris 95 generated during pressureshock waves treatment can be extracted through suction area 374 (inbetween the guide catheter 92 and the sheath 481), via a passive oractive suction. Concomitantly, saline solution is introduced intoenclosed chamber via “in” tubes 441, in order to create enough fluid toflush the debris 95.

Step (5) is similar to step (3), with the difference that the actionsare made in reversed order (after elimination of the occlusion 20 orblood clot, the tulip reflector” 490 is retrieved inside the sheath 481and the assembly is retrieved from the blood vessel 15 orgraft/artificial vessel 184 or natural conduit/lumen).

In Step (6) the introduction of saline solution via “IN” tubes 441 andextraction of saline solution with debris 95 occurs through the lumen ofthe guide catheter 92 few minutes after the end of the pressure shockwaves treatment to be sure that no debris 95 is left behind in the bloodvessel 15 or graft/artificial vessel 184 or natural conduit/lumen.

In step (7) the occlusion balloon 154 is deflated and the normalblood/fluid circulation is restored.

In step (8) the guide catheter 92 is retrieved from the blood vessel 15or graft/artificial vessel 184 or natural conduit/lumen.

The intracorporeal pressure shock waves catheter 340 (composed in thiscase out of the sheath 481, inner member 485 with the “tulip reflector”490 at its distal end), used for treating occlusions 20 and blood clots,may preferably use more than 2500 shots, energy flux densities higherthan 0.05 mJ/mm² and frequencies of the pulses higher than 2 Hz. Thedissolution (lysis) of the blood clots and destruction of occlusions 20can be done as an independent intracorporeal pressure shock wavestreatment or in conjunctions with specialized drugs and/orextracorporeal pressure shock waves devices.

Intracorporeal pressure shock waves may also be used to treathyperplasia, benign and malignant tumors or to produce cellularapoptosis. The intracorporeal pressure shock waves catheter 340 may alsobe used to treat hyperplasia (abnormal proliferation of cells thatproduces enlargement of organs). Hyperplasia needs to be treated becauseit can produce obstruction of the natural lumens (benign prostatichyperplasia or BPH can produce obstruction of the urethra), functionaldeficiencies of the organs/glands (as in adrenal hyperplasia), pain, orcan be an early neoplastic process that can lead to cancer.

For ablation of hyperplastic, benign or malignant tumors that can beaccessed via a natural conduit/lumen of the human or animal body 27 orby using an artificial conduits (laparoscopic approach), the mosttreatment technologies are radio-frequency, high intensity focusedultrasound or cryotherapy (usage of low/freezing temperatures). The maindrawback for these technologies is the extreme heat or freezingtemperatures generated during treatment that can affect adjacenttissues/organs and blood flow 39 circulation with unwanted side effects.After such procedures the absorption of ablated tissue by the body 27 ishindered by excessive inflammation, impaired blood circulation, fluidaccumulation, etc. produced by the extreme heat or freezing. Also, noneof these technologies are known to trigger a body reaction to heal thetreated area.

Cavitation bubbles produced by special tailored pressure shock wavescollapses with microjets powerful enough to penetrate the hyperplastic,benign or malignant cells membrane and thus destroying their integrity.This represents a “normal body temperature ablation” process notemploying high or low temperatures used by the existing ablationtechnologies and targets only the hyperplastic, benign or malignantcells without having damaging influences on the healthy adjacent tissue.

For the cancer cells, the leakage of the cytoplasm content outsidetriggers a localized apoptosis mechanism and an immune response, whichmakes the body 27 to recognize the cancer cells that were invisiblebefore and thus enhancing tumor destruction.

Pressure shock waves can be also used for treating cancer in conjunctionwith microparticles or/and nanoparticles, which can be activated orpushed into the tissue via pressure shock waves in order to selectivelykill cancer cells or to deliver specific drugs at high concentrationand/or proteins and/or substances that can destroy cancer cells.Furthermore, the pressure shock waves can be used to enhance thesensibility of the tumor cells to certain drugs and thus enhancing theircytotoxicity.

The construction of intracorporeal pressure shock waves catheter 340 isdone in such way to allow the formation, propagation and focusing of thepressure shock waves. The precise targeting of the tumor is done usingfluoroscopic or ultrasound guidance. Furthermore, in order to facilitatepropagation and focusing of the shock waves from the intracorporealpressure shock waves catheter 340 to the targeted tumor, saline and/orcontrast and/or drug cocktails can be injected in the treatment area vianatural conduits/lumens or percutaneously (artificial conduits).Examples of construction for the intracorporeal pressure shock wavescatheters 340 that can be used to ablate benign or malignant tumors andpromote apoptosis are shown in FIGS. 35, 36A, 36B, 39, 40, 41, 43, 44,45, 46, 47A, 47B, 47C, 49A, 49B, 49C, 49D and 49E.

The weeping balloons (with controlled porosity 415) shown in FIG. 41combined with pressure shock waves can be used to treat tissuemalformation that develop close or away from blood vessels 15 or naturalhuman/animal conduits/lumens. If such malformation or unwanted tissuegrowth is too far away from a blood vessel 15 or a bodycavity/conduit/lumen, then a percutaneously approach can be used (via asmall incision in the skin 28).

Based on the above observations, using a sufficient number of pressureshock waves (higher than 3500 shots), at energy flux densities higherthan 0.05 mJ/mm², with frequencies of the pulses between 1 to 8 Hz inone or multiple treatments applied to a hyperplastic/benign or malignanttumor a “normal body temperature ablation” can be realized usingextracorporeal pressure shock waves. The treatment ofhyperplastic/benign or malignant tumors can be done as independentintracorporeal pressure shock waves treatment or in conjunction withdrugs or drug cocktails that can be injected in the targeted treatmentarea and/or with other extracorporeal pressure shock waves devices.

Intracorporeal pressure shock waves may be used in embodiments of theinvention for “cold” liposuction and/or body sculpting. Liposuction isused to eliminate the excess fat from under the skin 28 in general inthe middle section of the body 27. A typical treatment includes the useof ultrasound to liquefy the fat and extracted via a wand. One bigdrawback of this technology is that ultrasound produces heat, whichhelps with the fat melting, but also can heat up the tip of the wand,which can produce sub-dermal burning, with important cosmetic andhealing drawbacks for the patient. This is why a technology that canavoid the heating and produce a “cold” melting is an improvement overliposuction or body sculpting.

Pressure shock waves produce cavitation and the microjets created by thecollapse of the cavitation bubbles can break the fatty cells and thefatty tissue in invention embodiments without producing localized excessheat that was observed with ultrasound. The micro-cracks in the fattytissue created by the microjets during collapse of the cavitationbubbles can be amplified by the compressive portion of the pressureshock waves and thus producing macro-tears of the fatty tissue, whichwill help to eliminate it during liposuction. These mechanisms are whythe pressure shock waves technology can be used to produce a “cold”liposuction, which eliminates the unnecessary side effects, observedwith the “Golden Therapy” that uses ultrasound technology.

A device that can be used for liposuction and body sculpting ispresented in FIG. 51.

The following characteristics are considerations for an intracorporealpressure shock waves device used to dissolve the fat cells inembodiments of the invention (as seen in FIG. 51, 52A and 52B):

-   -   1) Frontal exposure of the pressure shock waves reflectors        (ellipsoidal reflector 471 presented in FIG. 51, spherical        reflector 472 presented in FIG. 52A and bellowed reflector 473        presented in FIG. 52B), which are positioned at the distal end        of the treatment wand 515.    -   2) Cavitation is a preferable mechanism of action to break the        fat cells and fat deposits 512 in general. This mechanism why        the focal volume 108 (where the cavitation bubbles are formed)        for the applicators (471, 472 and 473) must intersect the fatty        cells clusters (fat deposits 512).    -   3) The dimensions of the reflector (471, 472 and 473) and its        optimal orientation (perpendicular to the targeted fatty tissue)        will dictate the efficiency of the intracorporeal pressure shock        waves.    -   4) The voltage used for actuating the applicators (471, 472 and        473) is in the range of millivolts to hundreds of volts.    -   5) If the actuating voltage for the intracorporeal pressure        shock waves reflectors (471, 472 and 473) is small enough,        battery operating devices can be developed.    -   6) The reflectors (471, 472 and 473) can be created from metal        or hard plastics or ceramics/glass and it sits at the distal end        of the treatment wand 515.    -   7) The method to produce pressure shock waves can be        electrohydraulic, electromagnetic, piezoelectric, laser        discharge, micro-explosion/discharge or mechanical vibrations,        with the pressure shock waves carried towards the target via an        aqueous environment.    -   8) The shape of the reflectors (471, 472 and 473) can be        elliptical, paraboloid, sphere or planar, or combinations of        them.    -   9) The construction of the wand 515 (metal wall) and the        associated plastic sheath 481 (made of plastic) preferably        allows electrical insulation of the patient and in the same time        a reduction in abrasion of the sub-dermal tissue.    -   10) The suction of fatty cells that were dissolved or broken        from the fatty clusters can be done via wand 515 or in between        the wand 515 and the sheath 481, which is defined as suction        area 374).    -   11) To increase efficiency a pivotal movement of the applicator        473 (as seen in FIG. 52B) will allow the orientation of the        cavitation on a larger area.    -   12) The electrohydraulic discharge, laser discharge or        micro-explosion/discharge should be made in degassed water or        saline solution or mixtures of saline solution with contrast,        enclosed in a special designed membrane 205 that allows the        formation of the cavitation cluster outside it.    -   13) To enhance the pressure shock waves transmission and the        possibility of the onset of in vivo cavitation, saline should be        injected in the front of the wand 515 to create a fluid layer in        between the applicators (471, 472 and 473) and the targeted        fatty cells.

When an ellipsoid is used the ratio of semi axes should be larger than2.0 (c/b≥2). In this way the focusing and formation of the cavitationwill be done at a sufficient distance in front of the applicators (471,472 and 473), with the whole focal volume 108 formed outside theapplicators (471, 472 and 473) and exclusively on the fatty cells. Ahigher ratio of semi axes will also allow having a deeper reflector(471, 472 and 473) incorporated into the tip of the treatment wand 515,which translates into a larger reflecting area and thus a higherefficiency. There is a direct correlation between the surface of theapplicators (471, 472 and 473) and the amount of energy deposited in thefocal volume 108. A larger reflecting area translates in higherefficiency for the pressure shock waves.

When a sphere is used as a reflector (FIG. 52A) radial waves 474 arecreated. Cavitation still may be created with radial waves 474, althoughthe penetration of the compressive waves is reduced, which will reduceeventual macro-tear in the fat deposit 512 after the onset ofmicro-cracks due to the cavitation microjets. The energy of the radialpressure waves 474 is the highest in the center of the sphere and itdissipates very fast during propagation away from the point of origin(center of the sphere).

When a significant amount of fat deposit 512 needs to be eliminated (fora successful liposuction and/or body sculpting) special designed suctioncatheters 93 or wands 515 or suction areas 374 (in between the interiorsurface of the sheath 481 and external surface of the treatment wand515) can be used via an active suction. The active suction is generatedby using dedicated pumps that continuously inject saline solution infront of the wand 515 and in the same time extract the mixture of debris95 generated during treatment (mixture of saline, fatty cells andblood). To facilitate an easy generation and propagation of the pressureshock wave s, the reflectors have a thin membrane 205 on top of themthat creates an enclosed space filled with degassed water. The water canbe filed at the manufacturer (pre-filled catheter) or can be done at thepoint of care. As can be seen from FIG. 51, 52A and 52 there are twodistinctive channels (inlet lumen 365 and outlet lumen 366) to fill inthe reflectors (471, 472 and 473). This construction also allows theclearing of air from the reflectors (471, 472 and 473). If air is notcleared, the efficiency of the pressure shock waves can be significantlyreduced.

FIG. 52B presents a pressure shock waves reflector (bellowed reflector473) which is movable in an angular fashion. The movement of thebellowed reflector 473 is realized by pulling at the proximal end of thewand 515 the two sutures (478 and 479) that run through the wand 515body and are connected to the lateral ears of the reflector. If suture478 is pulled (movement 522) then the bellowed reflector 473 will rotateupwards. If suture 479 is pulled (movement 524) then the bellowedreflector 473 will rotate downwards. The rotation takes place around the“living hinge” 477 through which the bellowed reflector 473 is connectedto the wand 515 body.

The bellows 476 act as a spring, which brings back the bellowedreflector 473 in straight position when the sutures are released fromthe tensional (pull) position.

The cavity of the reflectors (471, 472 and 473) is filled with degassedwater, medical saline solution or any mixture of fluids with additivesto enhance pressure shock waves formation and durability of theapplicators (471, 472 and 473) and wand 515.

When liposuction is accomplished with pressure shock waves devices, bothintracorporeal and extracorporeal devices can be used as seen in FIG.53. The two devices can be used concomitantly or sequential and they canbe con-focal (as seen in FIG. 53, where the focal volumes 108 intersect)or non-con-focal. The use of both devices can speed up the process ofdissolving the fat deposits 512 and thus is increasing the treatmentefficiency.

The pressure shock waves applicators (30 and 471) can be controlled bydifferent consoles or by one single console. The single console approachis preferable for high degree of coordination of focal volumes 108spatial placement (via longitudinal movement 31) for the externalapplicator 30 (in contact with skin 28)and the treatment wand 515(introduced under the skin 28 via small incisions). The sequence offiring the pressure shock waves into the treatment area between theexternal applicator 30 and internal applicator 471 can be coordinated toachieve maximum efficiency.

The settings for the intracorporeal pressure shock waves wand 515 usedfor liposuction should be for the dosage more than 5000 shots, at energyflux densities higher than 0.15 mJ/mm² and frequencies of the pulseshigher than 2 Hz.

The extraction of the mixture of debris 95 generated during treatment(mixture of saline, fatty cells and blood) is done via suction area 374created for the intracorporeal system in between the sheath 481 and wand515.

Embodiments of the invention also produce intracorporeal pressure shockwaves that are non-focused. If no reflector is used radial and planarnon-focused waves can be created. By eliminating the reflector more roomis created for the catheter inner construction, which can lead to theincrease in the energy delivered per one shock and also it makes thecatheter construction less complicated.

As shown in FIG. 54A and 54B, radial shockwaves can be generated by thedischarge in between the two electrodes in a balloon enclosure 541filled with degassed water or saline solution or salinesolution/contrast mixture, positioned at the distal end of theintracorporeal pressure shock waves catheter 340. The IN lumen 365 andOUT lumen 366 are used to fill in the space with degassed water orsaline solution or saline solution/contrast mixture, at requiredpressure and volume. OUT hole 547 provides a conduit to OUT lumen 366.

As shown in FIG. 54A, the uniformity of the discharge is accomplished bymaking one of the electrodes in the form of a sphere 542 (connected viaelectrical wire 432 to voltage source) and the other one as a wireelectrode 544, which facilitates an easy voltage discharge 546 anytimethe device is fired. The waves generated in such embodiment are radial474 and non-focused.

If a piezo crystals or piezo fiber or piezo films 551 are used togenerate the intracorporeal pressure shock waves inside a balloonenclosure 541 filled with degassed water or saline solution or salinesolution/contrast mixture, a planar wave 553 can be generated, as seenin FIG. 55A.

When a laser discharge 557 in degassed water or saline solution is usedinside a balloon enclosure 541, the laser will create a plasma bubblethat during its growth and collapse will be able to generate a radialwave 474, as can be seen also in FIG. 55B. Laser fiber 555 for laserdischarge 557 runs within catheter 340.

The embodiment of FIG. 55C depicts intracorporeal pressure shock wavescatheters 340 shown in FIGS. 55A and 55B, that have dedicateddistinctive channels (inlet lumen 365 and outlet lumen 366, withdifferent shapes when compared to the ones in FIG. 54B) that can be usedto fill in the balloon enclosure 541 and to allow the clearing of airfrom the intracorporeal pressure shock waves catheters 340. If air isnot cleared from the reflector, the efficiency of the pressure shockwaves can be greatly reduced.

For intracorporeal pressure shock waves catheters 340 shown in FIGS.54A, 54B, 55A, 55B and 55C, the waves will, in embodiments, travelwithout reflections if the materials used in the construction of theintracorporeal pressure shock waves catheters 340 have an acousticimpedance that matches/or is close enough to the water acousticimpedance value. As mentioned previously, the waves are generated insideballoon enclosure 541 inflated with degassed water or saline solution orsaline solution/contrast mixture. The balloon enclosure 541 can befilled at the manufacturer (pre-filled catheter) or can be done at the“point of care”. When the balloon enclosure 541 is pre-filled at themanufacturer, additional substances may be added into the water/salineto improve efficiency of the pressure shock waves generation andpropagation or for improved visualization of the intracorporeal pressureshock waves catheters 340 inside the human body 27 by using any contrastagents. Also, for easy visualization of the intracorporeal pressureshock waves catheter 340 inside the body 27, the tip 90 will be made ofradio-opaque materials and the position of the point of origin of thepressure shock waves can be identified via specific radio-opaque markers152 (bands, dots or combination of them). The radio-opaque markers 152,radio-opaque tips 90 combined with balloon enclosures 541 filled withmixtures of saline solution and contrast agents will allow the precisepositioning of the intracorporeal pressure shock waves catheter 340relatively to the treatment targeted area 145, under ultrasound orfluoroscopic guidance.

There are different methods to improve the efficiency and productivityof the pressure shock waves treatments and the majority focus ontreating a larger area and by increasing the amount of energy depositedinto the tissue in one position of the pressure shock waves applicators30.

Increasing the treated area in one position of the applicator 30 can beaccomplished by extending the focal volume 108 dimension or byintersecting the treatment targeted area 145 with focal volume 108longitudinally instead of transversally.

The amount of energy delivered to the focal volume 108 can be increasedby extending the reflective area of the reflector 22, by moving thepoint of origin/discharge of the pressure shock waves from F₁ on thedirection of F₁F₂ and thus creating a pseudo focal volume as anextension of the normal focal volume 108, or by overlapping multiplefocal volumes 108. Exemplary solutions are subsequently presented.

The theory of the pressure shock waves for medical treatment wasdeveloped for lithotripsy. Based on this theory, the ellipse has aunique property of having two focal points (F₁ and F₂), which can beinterconnected in energy generation and receiving.

Thus, if a 3D geometry is created (an ellipsoid) the kinetic energy (inthe form of pressure shock waves) generated in the first focal point Flwill be reflected with minimal loss in the second focal point F₂ whenthe whole ellipsoid surface is used. During focusing process of thepressure shock waves from F₁ to F₂, a focal volume 108 is created aroundF₂, with a cigar shape where high compressive pressures are generated(compressive phase 562 that produces macro effects) together with atensile phase 564 that produces cavitation (action at micro level), asseen in FIG. 56. The compressive phase start with a sharp rise inpressure characterized by the rise time 565 and the pulse width 566 (for−6 dB) determines the amount of energy deposited in the focal volume108.

The voltages used for discharge in Fi for electrohydraulic devices are12-30 kV. This discharge produces a plasma bubble in Fi that can rapidlymove the liquid around it to create pressure shock waves that are thenfocused on the full ellipsoidal reflector 471 to generate a sphericalfocal volume 108, as presented in FIG. 57A. Other ways to producepressure shock waves are electromagnetic, piezoelectric, explosive orprojectile means.

For the focused pressure waves, practically the full solid ellipsoid 571(whole ellipsoid) cannot be use to do a treatment with pressure shockwaves in F₂, based on the fact that the treatment area needs to bepositioned in F2 (see FIG. 57A). This is why in practice only half ofthe ellipsoid is used to generate and focus the pressure shock waves,towards F₂, as presented in FIG. 57B.

The amount of energy delivered to a target area is directly proportionalto the surface area of the reflector. As presented in FIGS. 57A, 57B,57C and 57D, in medical pressure shock waves applications the reflectorsrepresent only percentages of a full ellipsoid. The more area is usedfor focusing, the larger the focal volume 108 will be and thus energydeposited inside the treatment area.

Usually the most commons reflectors represent 50% of a full ellipsoid,which means that the available area for reflecting the pressure shockwaves is only 50%. That means that the pressure shock waves arereflected on only half of the surface and thus in theory only half ofthe energy is found in the focal volume 108, when compared to a fullellipsoid 571. Of course the efficiency is reduced below 50% due toother losses on the pathway of the pressure shock waves towards F2. Evenwith this reduced efficiency the treatments using extracorporealpressure shock waves were proven to be very efficacious for breakingkidney stones, or to treat bones and soft tissue afflictions.

As can be seen from FIG. 57B, when 50% of the ellipsoid area reflector572 is used the focal volume 108 is larger in size when compared to thefocal volume 108 of the 35% of the ellipsoid area reflector 573 fromFIG. 57C. Even more when 50% of the ellipsoid area reflector 574 is usedthe reduction in the focal volume 108 is even more significant, as seenfrom FIG. 57D. This shows that the smaller the available reflective areafor the pressure shock waves translates besides smaller quantities ofenergy in the treatment area as well as in smaller focal volumes 108,which finally means less efficiency for the treatment.

The pressure shock waves devices will generate a wide range of energiesin the focal volume 108 depending on reflector geometry, which ischaracterized by the ratio of “c” the large semi-axis of the reflectorand “b” the small semi-axis of the reflector (c/b), as can be seen fromFIGS. 58A, 58B and 58C.

The c/b˜1.1 geometry (FIG. 58A) in one embodiment has a shallowreflector that has F₂ very close to its edge and has less reflectivearea at its disposal. This geometry can be used to treat targets closeto the surface of the body 27 (underneath the skin 28) and with mediumto low energies.

The c/b˜1.6 geometry (FIG. 58B) may be used to treat targets deeperunderneath the skin 28 and has more reflective area at its disposal. Thetravel distance for the pressure shock waves is longer, which mightincrease losses. The energies generated are medium to high.

The c/b˜2 geometry (FIG. 58C) allows the treatment of deep structuresfrom inside the human body 27 and has the largest reflective area at itsdisposal, which translates in increased amounts of energy (high energy)deposited inside the tissue.

The c/b ratio or reflector area, voltage discharge in F₂, materials fromwhich the reflector is made and frequency of the shots (voltagedischarge) per second represent important parameters for generation ofpressure shock waves. All these parameters have a great influence on thedimensions of the focal volume 108 and the total energy deposited insidethe focal volume 108.

FIG. 59 shows that at the same depth of the reflector, one with a largeraperture area 592 (larger diameter) will produce higher pressures in thefocal volume 108, a larger focal volume 108 and a greater quantity ofenergy deposited in the treatment area. A reflector with smaller area591 when compared with the reflector with larger area 592, generates at“c/2” distance from the aperture a pressure gradient/distribution 593that is reduced when compared with the pressure gradient distribution594 generated by the reflector with larger area 592. The same phenomenonis recorded at the distance “c” from the aperture, where the pressuredistribution 595 for the reflector with smaller area 591 is reduced whencompared with the pressure gradient distribution 596 generated by thereflector with larger area 592. This trend is also found inside thefocal volume 109 where the pressure distribution 597 for the reflectorwith smaller area 591 is reduced when compared with the pressuregradient distribution 598 generated by the reflector with larger area592.

FIGS. 57A, 57B, 57C, 58A, 58B, 57C and 59 illustrate that the shallowerreflectors deposit less energy and at a smaller depth into the tissuecompared with the deeper reflectors that deposit more energy and at adeeper depth into the tissue, regardless of larger losses on the pathwayto the treatment targeted area.

Besides the dimension of the reflective area, another way to increaseefficiency of the pressure shock waves devices is to increase theirfocal volumes 108 by combining different geometries for the reflectors.Combinations of elliptical, paraboloid or sphere geometries can be usedin one reflector with combined geometries 600 having the spark gapdischarge 601 produced in F₁ (center of the sphere 604) for anelectrohydraulic system. In other embodiments a piezoelectric reflectorcan be constructed with piezo films, piezo fibers, or piezo crystalsarranged in the form of an ellipsoid 602, sphere 604, paraboloid or acombination of them, as shown in FIG. 60.

A reflector with combined geometries 600, including ellipsoidalreflector segment 605 and spherical reflector segment 606 can increasethe focal volume length by combination of the focal volume of theellipsoid segment 607 and focal volume of the sphere segment 608, whichcan cover more superficial or deep tissue during treatment. Thiscombination can increase the treatment efficiency for cosmeticapplications or for lymph-edema treatment for example.

Similar geometries can be also used with devices that produce pressureshock waves using electrohydraulic, electromagnetic, laser discharge,explosive, mechanical means.

To create improved reflectors a combination of ellipsoids 602, spheres603 and paraboloids can be used including: two geometries in onereflector (FIG. 60), or three or more geometries in one reflector.

In one embodiment, a preferred geometry for the ellipsoids used inreflectors with combined geometries 600 is given by ellipsoids generatedfrom ellipses with a semi axis ratio (c/b) between 1.1 and 1.5.

Such geometrical combinations can generate different types of pressureshock waves, including focused or unfocused, multiple and larger focalvolumes (607 and 608) and the like.

Due to combination of elliptical, parabolic or spherical geometries inone reflector, focal volume distribution is for the “reversed reflector”230 shown in FIG. 23A and FIG. 23B presents various embodiments of theinvention. In one embodiment, the reversed reflector 230 has a geometrysymmetrical around the small, axis of symmetry (FIG. 61B), which isdifferent from the classical reflector geometry 615 that uses the longaxis as axis of symmetry, as shown in FIG. 61A.

For the combination reflector of FIG. 60, a reversed reflector withcombined geometries 620 will be similar to the reflectors shown in FIGS.62A and 62B. The increased length of the focal volume, which in depictedembodiments is a combination of the focal volume 624 of the ellipsoidsegment 621 and focal volume 625 of the sphere segment 622 (see FIG.62A) or a combination of the focal volume 624 of the ellipsoid segment621 and focal volume 627 of the paraboloid segment 623 (see FIG. 62B)that creates a great advantage when the treatment is superficial.

Also, in embodiments presented in FIG. 62A reversed reflector 620generates in F₁ a radial wave 235 (produced by the spherical reflectorsegment 622) and in F₂ a focused wave, which means that this kind ofreflector has “dual pressure shock waves” (radial and focused). Thisduality can be beneficial for different phases of the treatment due tothe fact that radial pressure shock waves 235 have lower pressures andtissue penetration when compared to the focused waves that have higherpressures and tissue penetration. In embodiments presented in FIG. 62Bthe reversed reflector 620 includes a paraboloid reflector segment 623in combination with ellipsoidal segment 621.

Multiple (combined) reflectors 630 can be used to increase efficiency byincreasing focal volume 108, spatial distribution and overlap of thefocal volumes 108 in one position during the treatment, shown in FIG.63.

The discharge in F₁ can be done simultaneously or sequentially for thefour (4) reflectors in the depicted embodiment, which can be a settingin the software of the control console. The four (4) reflectors share acommon contact membrane 205 (not shown in FIG. 63) that gets in contactwith body appendage 25 or body 27 generally. The membrane 205 can bealso used to adjust tissue penetration in the order of millimeters byinflating and deflating it.

Another embodiment shown in FIGS. 64A and 64B includes an applicatorwith multiple reflectors 640 on two perpendicular directions producingoverlap of the focal volumes 108 on two perpendiculardirections/dimensions in the treatment area, which yields a threedimensional spread of the focal volumes 108. Due to the spatialorientation of the reflectors arranged on a spherical calotte dish 642,this embodiment creates a distribution of the focal volumes 108 on twodifferent and perpendicular directions, which is different from theembodiment presented in FIG. 63 where the focal volumes 108 align onlyin one direction. Each reflector has its independent electrodes 645 toproduce electrohydraulic generated pressure shock waves.

For a curved three-dimensional treatment area another embodiment can beused, wherein numerous reflectors 650 (with distinctive electrodes 645for spark discharge) are arranged on a half sphere dish 652 that createsa spatial distribution of the focal volumes 108, as shown in FIGS. 65A ,65B and 65C. Depending on the dish geometry (hemisphere, or a sphericalcalotte, or a semi-ellipsoid, or a paraboloid, or a cylinder) thespatial distribution of the focal volumes 108 can be modifiedaccordingly, depending on treatment scope. The flexibility of theseembodiments can be used to produce multi focal devices in the form ofbandages, boots, straps, braces, helmets, belts, etc., for increasedefficiency of the pressure shock waves treatments. Finally, thematerials used in the construction of such devices should bebiocompatible and/or sterilizable depending on the specific application.

Embodiments of the invention shown in FIGS. 65A, 65B and 65C use ahemisphere dish 652. Depending on the total energy that needs to bedelivered during one treatment and the depth inside the tissue where thefocal volumes 108 should be positioned during treatment for theapplicators presented in FIGS. 60, 62, 63, 64A, 64B, 65A, 65B and 65C atthe same diametric dimension of the reflector opening, the geometry ofthe reflector can be shallower (to deliver smaller energies intotreatment area and provide less tissue penetration) or deeper (forlarger energies deposited into treatment area and more tissuepenetration), as presented in FIGS. 57A, 57B, 57C, 57D, 58A, 58B, 58Cand 59.

FIGS. 66A and 66B show an embodiment where multiple reflectors 660arranged on a dish 642 that creates the spatial (3-D) distribution withall the focal volumes 108 found outside of the dish 642 and not insidethe dish 642, as shown in FIGS. 65A, 65B and 65C.

Another approach that provides flexibility and increased efficiency fortreatment with pressure shock waves applicators 30 (or any of thevariation and applicators special geometries presented in the body ofthis patent) is given by the automatically control of applicators'movements when necessary to change position in the course of onetreatment session.

A motorized holding fixture 674 may be provided for the multipleapplicators 675, as shown in FIG. 67. This holding fixture 674 iscontrolled by a computerized main console 670 that includes thecomponents that can generate pressure shock waves, user interface,security systems, power supply, high voltage cable 672 and software, asseen in FIG. 67.

The holding fixture 674 can be installed in embodiments on treatmenttable 676 and can offer flexibility of attaching one or more applicators675, as the specific treatment requires. Also, this fixture should beable to move applicators 675 on ±X, ±Y, ±Z, to focus the applicators 675on the desired treatment area. Additionally, the applicators 675 mayinclude angular movement around a hinge 128 mounted on the holdingfixture 674 that provides a pivoting axis 122 for the applicators 675,as shown in FIG. 68A. All these movements can be controlled by softwarebased on feedback from different sensors applied to the fixtures. Incertain embodiments, motors are the step motors that can be preciselycontrolled by software using angles values as part of rotationalmovement. DC or AC motors are other types of motors can also be used inother embodiments.

To achieve efficiency, a correct orientation of the applicators 675relatively to the treated area is maintained by keeping the axis of theapplicators 675 perpendicular to the plane of the targeted area. Theapplicators 675 orientation adjustments necessary during a treatment isrealized using step motors controlled by software that receivescontinuous feedback from the sensors' readings.

The automatic adjustment can be also done for individual applicators 675used in a manual movement during treatment provided by the physician(audible signals can be generated, which will trigger manual adjustmentsby the user) or can be used as part of an automatic fixture controlledby computer, as presented in FIG. 67.

Individual sensors 681 can be mounted directly on the sensors block 680of the applicators 675 (as seen in FIGS. 68A, 68B and 68C). The readingsfrom the sensors 681 mounted around the applicators 675 (two sensors 681and 682 at 180° apart as seen in FIG. 68A or three sensors 681, 682 and683 at 120° apart as seen in FIG. 68B or four sensors 681, 682, 683 and684 at 90° apart as seen in FIG. 68C) are averaged and compared. When asignificant difference occurs the adjustments are made by computer forautomatic fixtures or by the user in case of manual adjustment. For themanual adjustment, a beeper in the controlling console for theapplicators 675 might be triggered by the abnormal position, beeper thatstops when the correct position is finally found.

Schematic representation of positioning is presented in detail in FIGS.69, 70A, 70B and 70C. For the systems presented in FIGS. 68A, 68B, 68C,69 70A, 70B and 70C the sensors 681, 682, 683 and 684 are measuring thedistance to the target and the computer of main console 670 averages thereadings (from 2, 3 or 4 sensors that are present on sensors block 680).The averaged values can be compared with other averages from othersensors blocks 680 or against a preset nominal value and thus theposition of the applicators 675 can be corrected from a tilted position691 to the correct position as can be seen in FIGS. 69 and 70A-C.

Based on the sensors 681, 682, 683 and 684 readings and the computingalgorithm the adjustments are done “on the fly”, as presented in FIGS.70A, 70B and 70C. In the depicted embodiments, an exemplary algorithmfor triggering adjustment includes calculation of distances (L), (ι₁)and (ι₂). If L−ι₁=±1 mm no adjustment is considered necessary. If L−76 ₁is greater than 1.1 mm then adjustment is made to ι₂ to appropriatelylevel and correct the discrepancy. Similarly, if L−ι₂=±1 mm noadjustment is considered necessary. If L−ι₂ is greater than 1.1 mm thenadjustment is made to ι₁ to appropriately level and correct thediscrepancy for such side.

To optimize the process of treating larger areas (for example celluliteor burns) the software of the main console 670 can move the holdingfixture 674 for applicators 675 in optimum patterns (715 within area 712for applicator 675A and 717 within area 714 for applicator 675B) andthus adding the area treated by applicator 675A with the area treated byapplicator 675B, which translates in high efficiency for the treatmentwith minimal movement for the holding fixture 674, as shown in FIG. 71.

In such embodiment, the distance between applicators 675A and 675B headsis preferably larger than (1.5-2.0)×d, where d=diameter of theapplicators 675A and 675B.

The use of the holding fixture 674 for the sensors 681, 682, 683 and 684can also generate other advantages as presented in FIG. 72.

As seen from this embodiment, the holding fixture 674 for the applicator675 could contain pressurized reservoirs 722 with different liquids thatcan be sprayed during treatment over the skin 28 or targeted area 145(not shown in FIG. 72) from the body 27. The same liquid substances canbe pulverized via nozzles 724 on the treatment area using air and thuscreating aerosols. The medication combined with air movement can have onanalgesic effect. During one treatment, different substances can besprayed (via spray jets 726) on the treatment area based on necessitiesand physician's indications. Also, the front spray (placed in the frontof the applicator 675) could contain a different substance from the backspray (placed in the back of the applicator 675). Substances that mightbe used with this design can be analgesics, antibiotics, salinesolution, liquid gel, and the like.

On treatments performed on body appendages 25 (smaller areas whencompared to the torso) manual coordination/positioning of theapplicators 675 may be utilized in some embodiments. To avoid themisalignment of the applicators 675 to the treatment area (applicators675 are non-perpendicular per targeted surface), the applicators 675 canbe mounted in a special designed holder, to provide stability and goodalignment. The whole concept is based on creating a plane by having atleast three (3) points of contact with the skin 28. The laws of geometrystate that at least 3 points (731, 732 and 733) can determine/define aplane 735 and its position in space, as presented in FIG. 73 (Priorart).

Based on this theory, the holder will have three points of contact withthe skin 28 (thus creating a stable plane 735) and in the middle of theplane 735 the applicator 675 will be held in place, in the rightposition to the treatment areas (F2 in the treatment zone without tiltsof the applicator that can modify focal zone positioning relatively tothe skin 28 and the correct deposit of treatment energy in the treatmentarea).

Based on this theory, the applicator 675 may be a special designedapplicator holder 740, as presented in FIG. 74A and 74B. From thisfigure it can be seen that a>b with the longitudinal movement of theassembly along the “a” dimension shown by the black arrow.

This applicator embodiment can be used for extended treatment areasespecially on body appendages 25 (small and curved surfaces).Embodiments of the invention can be used in non-limiting examples on thetorso, buttocks and for the front of body 27. The applicator 675 staysin place due to its own weight (G) and under the force (F) that the userapplies on applicator 675 during treatment.

As shown in FIGS. 74A and 74B, the applicator holder 740 holds theapplicator body 742, which allows the correct positioning of theapplicator reflector cavity 745 relative to the body appendage 25 orbody 27 generally. The applicator reflector cavity 745 is isolated withthe membrane 205, which also facilitates the smooth contact with thebody appendage 25 or body 27 generally.

The applicator holder 740 can be delivered in different versions thatallow the reflector cavity 745 and membrane 205 (marked as 745 on theFIGS. 75A, 75B and 75C) to have the contact 754 in the same plane (seeFIG. 75A) nested by the holder 740 three (3) points 743 (defining holderplane 752) of contact or in another plane—such as after the plane (aspresented in FIG. 75B) or before the plane (as can be seen from FIG.75C). Holder contact points 743 may include rollers, wheels and likeelements for movement of the holder 740 in embodiments of the invention.

To accomplish the positioning of the reflector cavity 745 and membrane205 in the holder plane 752 or before or after holder plane 752, theholder 740 can be provided in different embodiments, based on thetargeted treatment area that dictates the necessary penetration depthinside the body 27. Using fixed reflector geometry, when the contact 754with the body 27 is made after the holder plane 752 a deeper penetrationis accomplished. For shallower penetrations the contact of the contact754 with the body 27 is made before the holder plane 752.

To accomplish the variability in tissue penetration, a holder 740 inembodiments includes a latch mechanism or a screw-nut mechanism toadjust where the contact 754 with the body 27 is made (“before”, “in” or“after” the holder plane 752).

Much larger areas of treatment embodiments may utilize in embodiments a“bracelet design” 780 (FIGS. 78A and 78B), which includes attachingmultiple applicators 675 sitting in holders 740. The holders 740 for thebracelet design 780 are connected, such as in non-limiting embodimentsvia female ball hinges 765 combined with male ball hinges 767, thatallow the applicators 675 and associated holders 740 to interconnect(FIGS. 76A and 76B). For these holders 740, two points 743 of the holderplane 752 come from the holder body 747 and the third point is given bythe applicator contact 754 with the body 27, as seen in FIG. 76A. Thismeans that the applicator 675 is preferably in the holder plane 752.

In FIG. 77, α and β are the possible angles of rotation for consecutiveholders 740 (only the holder body 747 seen in the FIG. 77 and notincluding the entire holder assembly 740) to allow their relativemovement in the female ball hinges 765 and male ball hinges 767 area, inorder to conform to the body 27 curves.

In FIGS. 78A and 78B, the “bracelet design” 780 is presented in furtherdetail. The smaller “L” distance between consecutive holder bodies 747,the smaller the distance that the bracelet design 780 needs to be movedlongitudinally (“bracelet” chain secondary movement 788). Thetransversal movement (main movement 787) will be with a distance equalto the diameter of the focal volume 108 (not the same as applicator'sdiameter “d”). The combination of the main movement 787 and secondarymovement 788 gives the movement pattern 786 of the bracelet design 780in the treatment area 784.

The shape of holder bodies 747 can be a triangle or any other shape thatfacilitates a stabilizing plane combined with hinge connection(connection points 782).

Holder bodies 747 preferably stay close to the body 27 and theconnection to the applicators 675 is preferably as close as possible toapplicator's distal end (in the applicator reflector cavity 745 area).

The connection of the applicators 675 to the body 27 occurs in variousembodiments via gels or gel pads 52 designed to conform to bodycurvature and to control tissue penetration (thicker gel pads 52 canreduce tissue penetration and vice versa).

The stability is again realized with the applicator's 675 own weight (G)and the force F that the user can apply on applicator 675 (FIGS. 74A and74B).

As illustrated in FIG. 78B, the bracelet design 780 can be used with acomputerized system, such as depicted in FIG. 67, where the twodimensional movements of the connected applicators 675 (main movement787 perpendicular on the axis of the bracelet assembly and the secondarymovement 788 along the axis of the bracelet assembly) is controlled viaa dedicated software. The computerized movement pattern 786 can be donein any geometry and kinds of directions of motion, including beyond theembodiments of FIGS. 71, 78A and 78B. For example, a spiral movement canbe used to uniformly cover a treatment area in other embodiments.

Another approach to increase the treatment area in one applicator 675position is given by the increase of the cross-section of the focalvolume 108 in a tangential direction (parallel to the skin 28). Thereflector geometry can be “reversed” as shown in FIGS. 79A and 79B (withfurther reference to FIGS. 23A, 23B, 61A and 61B).

The reversed reflector 800 embodiment presented in FIG. 80 has thefollowing advantages:

-   -   A radial pressure shock waves is generated from Fi at electrode        805 where the high voltage discharge is produced, due to the        fact that the radial wave 621 that propagates below the        reflector does not have any surface to bounce back. Thus the        waves propagate into a body 27 in the treatment area.    -   Focused pressure shock waves are also produced by the radial        wave 795 generated in F₁ and is reflected by the upper portion        of the reflector and then focused towards F₂.    -   Treatment area longitudinally slices the focal volume 108 and        not transversally as with classic reflector designs, which also        translates into increased efficiency of the treatment in one        fixed position.

The reversed reflector 800 has the advantage in various embodiments ofcreating radial and focused pressure shock waves in the treatment areausing only one reflector. The “double punch” pressure shock waves canincrease the efficiency of the treatment for superficial areas of thebody 27 such as wounds, burns, cellulite, and the like.

Another embodiment includes a “pipe reflector” 810 shown in FIG. 81,which has multiple focal points of electrodes 815 and focal volumes 108,to increase the area that is treated in one position of the reflector(the summation of multiple focal volumes 108). A reduction of thesurface of reflection for the pressure shock waves (only slices of thehalf ellipsoid are used) is expected to reduce the energy delivered bythe pressure shock waves in each individual focal volume 108 incomparison to classical design (half ellipsoid). Such embodiments arebeneficial for longer treatment areas that require low energies to bedeposited into the tissue.

Another embodiment for generating pressure shock waves includes creatinga movable pressure shock waves electrode (pressure shock wavesoriginating source), which can be moved out of focus (move up or downfrom Fi that represents the normal geometrical position for the firstfocal point of an ellipsoid). In this way a change in the geometry ofthe focal volume 108 can be achieved.

A shift in the spark discharge 601 produces (for both −z and +z) achange in the second focal point from geometrical F₂ to a pseudo focalpoint F₂′.

From a focal shift, a change in pressure distribution and values in thefocal volume 108 will be reflected in modification of energy values andtheir distribution. For an electrohydraulic device this means that witha certain voltage discharge in F₁′, different levels of energies can beachieved in F₂ and F₂′, when compared with normal discharge in F₁.

The advantages of generating different energy values in F₂ and differentenergies' distributions in the focal volume 108 (normal and extended)using the same voltage discharge in Fi or in the shifted point F₁′include simplified construction of control console and possibility totune the energy for many treatments using one range of dischargevoltages.

Simulation with COMSOL acoustic propagation software package shows thefollowing results (for all corresponding figures the top image (A) showsis showing pressure amplitudes correlated with the pressure shock wavesfront propagation and the bottom image (B) shows the 2-D view of the topimage):

FIGS. 82A and 82B shows the normal discharge in geometrical focal pointF₁, which is starting the pressure shock waves propagation 825 towardsthe second geometrical focal point F₂.

FIGS. 83A and 83B shows the reach of the pressure shock waves 835 in thesecond geometrical focal point F₂ after a normal discharge in the firstgeometrical focal point F₁. High amplitude pressures are generated inF₂, where the bottom peak represents the compressive pressurecorresponding to compressive phase and the top one the negative pressurecorresponding to tensile phase that generates cavitation.

FIGS. 84A and 84B shows the discharge at a shifted point F₁′ (22 mm upfrom the first geometrical point F₁), which is starting the pressureshock waves propagation 845 towards the second geometrical focal pointF₂ and pseudo second focal point F₂′, symmetric to F₁′ regarding thesmall semi-axis of the ellipsoid.

FIGS. 85A and 85B shows the movement of the primary shock waves front845 towards the F₂′ and F₂ and the reflection at the bottom of thereflector, which creates a secondary shock waves front 855, which has alarge delay from the primary shock waves front and has enough energy toproduce a pressure spike when will pass through F₁.

FIGS. 86A and 86B shows the secondary shock waves front (shown in FIGS.85A and 85B) passing through F₁, which due to the spike in pressure 867acts as a secondary pressure source for a new wave front (tertiary shockwaves pressure front 875) with the origin in F₁. Also a spherical wave865 is generated by the reflector's right edge/top rim.

FIGS. 87A and 87B shows the spatial distribution and the time delaybetween the primary shock waves front (passing through F₂ with no spikein pressure), secondary shock waves front (almost a straight linestarting to interfere with the reflector's right top rim wave shown inFIGS. 86A and 86B) and the tertiary shock waves front 875.

FIGS. 88A and 88B shows the reach of the secondary shock waves front inF₂′ (pseudo second focal point), which shows significant pressure spikes885. Also as seen from FIGS. 86A-87B, the secondary shock waves front855 brings significant increases in pressure between F₁ and F₂′, whichsuggests increased focal volume length. A secondary shock waves front872 is shown that originates from the left side of the reflector.

FIGS. 89A and 89B shows the reach of secondary shock waves front in F2resulting in pressure spike 897. The “remaining secondary shock wavefront” 893 formed by interaction of secondary front with the waveproduced by reflector's right top rim is pushed away from the axis ofthe reflector by the tertiary front and the front from left sidereflector's rim 895.

FIGS. 90A and 90B shows the formation of two new fronts from the top rimof the reflector (secondary 903 and tertiary 905), produced by theinteraction with remaining secondary shock waves front shown on FIGS.89A and 89B and with the tertiary wave. The short delay between thesefronts makes them prone to interaction.

FIGS. 91A and 91B shows the interaction 913 of secondary and tertiarywaves close to pseudo focal point F₂′. Due to their small time delay thetwo waves were pushed into each other by the wave coming from leftproduced by reflector's rim from the left side (see FIGS. 90A and 90B).A new (secondary) spike 915 in pressure results.

FIGS. 92A and 92B shows that the spike 925 in pressure observed in FIG.91A and 91B becomes significant when it reaches F₂′ (the second pseudofocal point). That means that besides focal volume 108 extension alongthe F₁F₂ axis, a secondary spike in pressure can be seen in F₂′ (thefirst one was seen in FIG. 88).

FIGS. 93A and 93B shows that the 935 spike in pressure observed in FIGS.92A and 92B continues to be seen when it reaches F₂ (the secondgeometrical focal point), which confirms the focal volume 108 extensionalong the F₁F₂ axis.

The foregoing results and graphs show significant difference between thedischarge in F₁ and in F₁′ including:

-   -   10 ns after discharge a difference in spatial distribution of        the discharge between normal discharge in F₁ and the shifted        discharge in F₁′ is visible.    -   The direct wave and reflected wave can be clearly distinguished.        The time delay between waves is dictated by the distance between        the discharge points to the bottom of the reflector.    -   The reflected wave (that follows closely the direct compression        wave) gets distorted due to the reflections on the edge of the        reflector. Also, the focusing occurs after the wave passes the        edge of the reflector.    -   The simulation shows that a discharge in F₁′ creates a symmetric        focal point F₂′ situated before F₂ (normal geometric second        focal point). Also, there are two distinctive peaks that pass        through F₂′—the first one at 50-60 μs after discharge and the        second one at 90 μs. Also, the pressure values are lower than        the pressure values generated in the normal way when the        discharge takes place in F₁.

The focal volume 108 seems to be enlarged when the discharge takes placein F₁′ or at least shifted with the distance between F₁ and F₁′. Highpressures are developed before F₂′ and in between F₂′ and F₂.

These observations and the interaction shown from the graphs of FIGS.82A-93B suggest with reference to FIGS. 94A and 94B:

Desirable focusing is realized with the normal discharge in F₁ (941)(normal first geometric focal point of the ellipsoid), resulting inpressure distribution 947 in focal volume 108.

Referring to FIGS. 94A and 94B, a discharge away from F₁ (941) atdischarge point 943 (FIG. 94B) and on the F₁F₂ line creates focusedpressure shock waves in a pseudo focal point F₂′ (949) symmetric withthe small axes of symmetry of the ellipsoid. High pressures are stillpresent in F₂ (although smaller when compared with the normal dischargein the first geometrical focal point F₁), which suggests an elongationof the focal volume 108 or an overlap between a reduced normal focalvolume 108 with a pseudo focal volume 945.

In F₂′ there are two distinctive pressure shock waves, a primary one 948in focal volume 108 generated by the discharge in F₁′ and a secondaryone 949 in pseudo focal volume 945. The second wave seems to be acomplex interaction of waves oriented from the edge of the reflectortowards the pseudo focal point F₂′.

The amount of energy (connected to pressure values show in FIGS.82A-93B) seems to be lower in the pseudo focal volume 945 centered inF₂′ when compared to the energy in the focal volume 108 centered in F₂generated by the normal discharge in F₁. A defocused discharge reducesthe amount of energy in the corresponding second focal point. If adischarge of 20 kV is used in the first pseudo focal point (F₁′) theamount of energy in the second focal point (F₂) and the second pseudofocal point (F₂′) may be similar to a 15 kV discharge. A broader rangeof energy can be delivered during treatment using a narrow dischargerange for the controlling device. In other words with a 20-28 kV highvoltage source, it can be delivered in F₂ and F₂′ energies equivalent to8-18 kV, when shifting from F₁ to F₁′.

The change in focal volume 108 combined with an increased range ofenergies that can be delivered for the treatment using the same sourceand reflector geometry, represents two advantages of focal pointshifting.

The movement of the electrode 955 inside a reflector with classicalgeometry 615 as shown in FIG. 95 can be done manually or automaticallyusing an adjustment mechanism 950 such as a screw/nut mechanism, a gearmechanism, sliding mechanism and the like.

The change in focal volume 108 dimension and the enlargement of thebandwidth of energies that can be delivered using a unique high voltagesource, and one reflector geometry may be beneficial for treatmentsusing pressure shock waves.

For example, sometimes it is difficult to provide a properelectrohydraulic discharge of voltages lower than 16 kV. The variationfrom shock to shock can be higher than 50%. By using the shifted focusthe discharge can be produced at 20 kV (which provides a more repeatableand consistent discharge) with the advantage of delivery in F₂′ anenergy equivalent to a 16 kV discharge, other new treatments requiringlower energies from a few kilowatts up to 18 kV may be facilitated.

The high voltage discharge from 18 kV to 30 kV used in conventionalelectrohydraulic devices and are capable of providing the energyrequired for pressure shock waves treatments. With a shifted discharge,the range of treatments can range from a few kilovolts up to 30 kV,using one of the existing/commercial available high voltage sourcesincorporated in the existing commercial available devices.

The foregoing approaches can also be applied in embodiments withreversed reflector geometry 804 as shown in FIG. 96.

In a reflector with reversed reflector geometry 804, the area treated inone shock is much larger due to the fact that the treatment area iscrossed longitudinally by the focal volume 108 instead of transversely.The significant longitudinal increase in the focal volume 108 length(due the combination of normal focal volume 965 with pseudo focal volume967) may further improve the efficiency of the treatment for superficialtreatment areas. Specifically, electrode 961 (F₁) shifted to selectivelygenerate shock waves at electrode position 962 (F₃) may shift normalfocal volume 965 into a pseudo focal volume 967 that intersect the bodycontact plane 807. Volume 965 arises from wave front 963 that originatesat electrode 961 and pseudo focal volume 967 arises from wave front 964that originates at electrode 962. In the reverse reflector embodiment ofFIG. 96, the longitudinal axis of symmetry 803 of the ellipsoid 801 isshown to intersect all points F₁-F₄ without coinciding with the contactplane 807. This improved efficiency translates in reduced number ofmovements per treatment necessary to cover a large treatment area.

While the invention has been described with reference to exemplarystructures and methods in embodiments, the invention is not intended tobe limited thereto, but to extend to modifications and improvementswithin the scope of equivalence of such claims to the invention.

What we claim is:
 1. An intracorporeal pressure shock wave apparatuscomprising: a catheter sized to fit within a human or animal bloodvessel or body lumen; an expandable and retractable pressure shock wavereflector coupled at a distal end of the catheter to direct pressureshock waves; and a pressure shock wave generating device adjacent thepressure shock wave reflector.
 2. The intracorporeal pressure shockapparatus device of claim 1, wherein the pressure shock wave reflectoris foldable.
 3. The intracorporeal shock wave apparatus of claim 2,wherein the pressure shock wave reflector includes a plurality ofleaves.
 4. The intracorporeal shock wave apparatus of claim 1, whereinthe pressure shock wave generating device together with the pressureshock wave reflector in expanded state are configured to produce focusedpressure shock waves.
 5. The intracorporeal pressure shock waveapparatus of claim 4, wherein the pressure shock wave reflector isfoldable and includes a plurality of leaves.
 6. The intracorporeal shockwave apparatus of claim 5, further comprising an occlusion ballooncoupled to the catheter.
 7. The intracorporeal shock wave apparatus ofclaim 6, further comprising a radio-opaque marker coupled to thecatheter configured to provide positioning of the shock wave reflectorin combination with fluoroscopy.
 8. The intracorporeal shock wave deviceof claim 7, wherein the pressure shock wave reflector is crimped to aninner member within the catheter.
 9. The intracorporeal shock waveapparatus of claim 8, wherein the pressure shock wave generating deviceincludes at least one of a laser configured to provide anelectrohydraulic shock wave discharge and piezoelectric material layeron the pressure shock wave reflector.
 10. The intracorporeal shock waveapparatus of claim 9, further comprising a forward and backward movablesheath within the catheter, wherein said sheath covers the pressureshock wave reflector in a retracted state.
 11. The intracorporeal shockwave apparatus of claim 10, further comprising a thin polymeric membraneon the outside of the shock wave reflector controlling extension of theleaves under dynamic pressure generated by pressure shock waves from thepressure shock wave generating device.
 12. The intracorporeal shock waveapparatus of claim 11, wherein the catheter includes a suction areabetween the catheter and the sheath.
 13. The intracorporeal shock waveapparatus of claim 12, wherein the reflector includes at least one ofnitinol and another temperature memory metal.
 14. The intracorporealshock wave apparatus of claim 4, further comprising a radio-opaquemarker coupled to the catheter configured to provide positioning of thepressure shock wave reflector in combination with fluoroscopy.
 15. Theintracorporeal pressure shock wave apparatus of claim 14, wherein thepressure shock wave reflector is foldable and includes a plurality ofleaves, and further comprising a forward and backward movable sheathwithin the catheter, wherein said sheath covers the pressure shock wavereflector in a folded state.
 16. The intracorporeal pressure shock waveapparatus of claim 15, further comprising a thin polymeric membrane onthe outside of the pressure shock wave reflector controlling extensionof the leaves under dynamic pressure generated by pressure shock wavesfrom the pressure shock wave generating device.
 17. The intracorporealpressure shock wave apparatus of claim 16, wherein the pressure shockwave reflector includes at least one of nitinol and another temperaturememory metal.
 18. The intracorporeal pressure shock wave apparatus ofclaim 15, wherein the catheter includes a suction area between thecatheter and the sheath.
 19. The intracorporeal pressure shock waveapparatus of claim 18, further comprising an occlusion balloon coupledto the catheter.
 20. An intracorporeal pressure shock wave apparatuscomprising: a catheter sized to fit within a human or animal bloodvessel or body lumen; a foldable pressure shock wave reflector includinga plurality of leaves coupled at a distal end of the catheter to directpressure shock waves; a forward and backward movable sheath within thecatheter, wherein said sheath covers the pressure shock wave reflectorin a folded state; an inner member within the sheath crimped to thefoldable pressure shock wave reflector; a radio-opaque marker coupled tothe catheter configured to provide positioning of the pressure shockwave reflector in combination with fluoroscopy; a suction area betweenthe catheter and sheath; an occlusion balloon coupled to the catheter;and a pressure shock wave generating device adjacent the pressure shockwave reflector.